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However, the underlying mechanisms of IDD remain poorly understood, necessitating further investigation. Environmental risk factors, such as mechanical stress and cigarette smoke, elevate reactive oxygen species levels from both endogenous and exogenous sources, leading to redox imbalance and oxidative stress. The endoplasmic reticulum (ER) and mitochondria, two key organelles responsible for protein folding and energy production, respectively, are particularly vulnerable to oxidative stress. Under oxidative stress conditions, ER stress and mitochondrial dysfunction occur, resulting in unfolded protein response activation, impaired biosynthetic processes, and disruptions in the tricarboxylic acid cycle and electron transport chain, ultimately compromising energy metabolism. Prolonged and excessive ER stress can further trigger apoptosis through ER\u2013mitochondrial crosstalk. Given the unique microenvironment of the intervertebral disc (IVD)\u2014characterized by hypoxia, glucose starvation, and region-specific cellular heterogeneity\u2014the differential effects of environmental stressors on distinct IVD cell populations require further investigation. This review explores the potential mechanisms through which environmental risk factors alter IVD cell activities, contributing to IDD progression, and discusses future therapeutic strategies aimed at mitigating disc degeneration.<\/jats:p>","DOI":"10.3390\/cells14080613","type":"journal-article","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T20:31:36Z","timestamp":1745181096000},"page":"613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["REDOX Imbalance and Oxidative Stress in the Intervertebral Disc: The Effect of Mechanical Stress and Cigarette Smoking on ER Stress and Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"14","author":[{"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Clemson University, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Clemson University, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Physical Medicine & Rehabilitation, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Academic Magnet High School, North Charleston, SC 29405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-8850","authenticated-orcid":false,"given":"Zhi-Wei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyelle M.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-2955","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-8528","authenticated-orcid":false,"given":"Yongren","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Clemson University, Charleston, SC 29425, USA"},{"name":"Department of Orthopaedics and Physical Medicine & Rehabilitation, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xu, S., Chen, J., Wang, C., Lin, Y., Huang, W., Zhou, H., Ji, W., and Chen, Y. (2025). Global, Regional, and National Burden of Low Back Pain for Adults Aged 55 and Older 1990\u20132021: An Analysis for the Global Burden of Disease Study 2021. BMC Musculoskelet. Disord., 26.","DOI":"10.1186\/s12891-025-08326-3"},{"key":"ref_2","first-page":"21","article-title":"Lumbar Disc Disorders and Low-Back Pain: Socioeconomic Factors and Consequences","volume":"88","author":"Katz","year":"2006","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1231","DOI":"10.1002\/jsp2.1231","article-title":"Intervertebral Disc Degeneration and How It Leads to Low Back Pain","volume":"6","author":"Diwan","year":"2022","journal-title":"JOR Spine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1026","DOI":"10.1002\/jsp2.1026","article-title":"Mechanotransduction and Cell Biomechanics of the Intervertebral Disc","volume":"1","author":"Fearing","year":"2018","journal-title":"JOR Spine"},{"key":"ref_5","first-page":"181","article-title":"Role of Oxidative Stress in Mitochondrial Dysfunction and Their Implications in Intervertebral Disc Degeneration: Mechanisms and Therapeutic Strategies","volume":"49","author":"Zhou","year":"2024","journal-title":"J. Orthop. Transl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00441-019-03136-1","article-title":"Mechanobiology of Annulus Fibrosus and Nucleus Pulposus Cells in Intervertebral Discs","volume":"379","author":"Molladavoodi","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/jor.20927","article-title":"Relationship between Solute Transport Properties and Tissue Morphology in Human Annulus Fibrosus","volume":"27","author":"Travascio","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jmbbm.2017.01.037","article-title":"Biomechanics of the Human Intervertebral Disc: A Review of Testing Techniques and Results","volume":"69","author":"Newell","year":"2017","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1294","DOI":"10.1002\/jsp2.1294","article-title":"Cartilaginous Endplates: A Comprehensive Review on a Neglected Structure in Intervertebral Disc Research","volume":"6","author":"Crump","year":"2023","journal-title":"JOR Spine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Buchweitz, N., Sun, Y., Cisewski Porto, S., Kelley, J., Niu, Y., Wang, S., Meng, Z., Reitman, C., Slate, E., and Yao, H. (2024). Regional Structure-Function Relationships of Lumbar Cartilage Endplates. J. Biomech., 169.","DOI":"10.1016\/j.jbiomech.2024.112131"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Richardson, S.M., Ludwinski, F.E., Gnanalingham, K.K., Atkinson, R.A., Freemont, A.J., and Hoyland, J.A. (2017). Notochordal and Nucleus Pulposus Marker Expression Is Maintained by Sub-Populations of Adult Human Nucleus Pulposus Cells through Aging and Degeneration. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01567-w"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/nyas.13964","article-title":"Annulus Fibrosus Cell Phenotypes in Homeostasis and Injury: Implications for Regenerative Strategies","volume":"1442","author":"Torre","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fu, F., Bao, R., Yao, S., Zhou, C., Luo, H., Zhang, Z., Zhang, H., Li, Y., Yan, S., and Yu, H. (2021). Aberrant Spinal Mechanical Loading Stress Triggers Intervertebral Disc Degeneration by Inducing Pyroptosis and Nerve Ingrowth. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80756-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e52570","DOI":"10.7554\/eLife.52570","article-title":"P16 Deficiency Attenuates Intervertebral Disc Degeneration by Adjusting Oxidative Stress and Nucleus Pulposus Cell Cycle","volume":"9","author":"Che","year":"2020","journal-title":"eLife"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fewster, K.M., Noguchi, M., Gooyers, C.E., Wong, A., and Callaghan, J.P. (2020). Exploring the Regional Disc Bulge Response of the Cervical Porcine Intervertebral Disc under Varying Loads and Posture. J. Biomech., 104.","DOI":"10.1016\/j.jbiomech.2020.109713"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mohd Isa, I.L., Teoh, S.L., Mohd Nor, N.H., and Mokhtar, S.A. (2022). Discogenic Low Back Pain: Anatomy, Pathophysiology and Treatments of Intervertebral Disc Degeneration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010208"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ziaf016","DOI":"10.1093\/jbmrpl\/ziaf016","article-title":"Endplate Remodeling: A Key Indicator of Cigarette Smoke Exposure-Induced Intervertebral Disc Degeneration in a Male Rat Model","volume":"9","author":"Kelley","year":"2025","journal-title":"JBMR Plus"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Seo, Y.-S., Park, J.-M., Kim, J.-H., and Lee, M.-Y. (2023). Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants, 12.","DOI":"10.3390\/antiox12091732"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maldonado, E., Morales-Pison, S., Urbina, F., and Solari, A. (2023). Aging Hallmarks and the Role of Oxidative Stress. Antioxidants, 12.","DOI":"10.3390\/antiox12030651"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e70015","DOI":"10.1002\/jsp2.70015","article-title":"Effect of Cigarette Smoke Exposure and Cessation on Regional Diffusion Properties in Rat Intervertebral Discs","volume":"7","author":"Kelley","year":"2024","journal-title":"JOR Spine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Zhang, L., Zhou, L., Lei, Y., Zhang, Y., and Huang, C. (2019). Redox Signaling and Unfolded Protein Response Coordinate Cell Fate Decisions under ER Stress. Redox Biol., 25.","DOI":"10.1016\/j.redox.2018.11.005"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.freeradbiomed.2020.12.007","article-title":"Redox Signaling, Mitochondrial Metabolism, Epigenetics and Redox Active Phytochemicals","volume":"179","author":"Wu","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.bbagen.2014.11.010","article-title":"Oxidative Stress, Redox Regulation and Diseases of Cellular Differentiation","volume":"1850","author":"Ye","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1016\/j.molcel.2021.08.018","article-title":"Redox Metabolism: ROS as Specific Molecular Regulators of Cell Signaling and Function","volume":"81","author":"Lennicke","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrm3801","article-title":"Cellular Mechanisms and Physiological Consequences of Redox-Dependent Signalling","volume":"15","author":"Finkel","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13448","DOI":"10.1111\/cpr.13448","article-title":"Oxidative Stress in Intervertebral Disc Degeneration: Molecular Mechanisms, Pathogenesis and Treatment","volume":"56","author":"Wang","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Choi, S. (2018). Sulfiredoxin. Encyclopedia of Signaling Molecules, Springer International Publishing.","DOI":"10.1007\/978-3-319-67199-4_194"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.freeradbiomed.2018.03.038","article-title":"An Evolving Understanding of the S-Glutathionylation Cycle in Pathways of Redox Regulation","volume":"120","author":"Zhang","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of Oxidative Stress as an Anticancer Strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1021\/cr300163e","article-title":"Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery","volume":"113","author":"Paulsen","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, D., He, X., Zheng, C., Wang, C., Peng, P., Gao, C., Xu, X., Ma, Y., Liu, M., and Yang, L. (2022). Endoplasmic Reticulum Stress: An Emerging Therapeutic Target for Intervertebral Disc Degeneration. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.819139"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1111\/febs.14972","article-title":"Impaired Calcium Homeostasis via Advanced Glycation End Products Promotes Apoptosis through Endoplasmic Reticulum Stress in Human Nucleus Pulposus Cells and Exacerbates Intervertebral Disc Degeneration in Rats","volume":"286","author":"Luo","year":"2019","journal-title":"FEBS J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8880320","DOI":"10.1155\/2020\/8880320","article-title":"Mitochondrial Dysfunction in Intervertebral Disc Degeneration: From Pathogenesis to Therapeutic Target","volume":"2020","author":"Li","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cheng, F., Yang, H., Cheng, Y., Liu, Y., Hai, Y., and Zhang, Y. (2022). The Role of Oxidative Stress in Intervertebral Disc Cellular Senescence. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1038171"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Silwal, P., Nguyen-Thai, A.M., Mohammad, H.A., Wang, Y., Robbins, P.D., Lee, J.Y., and Vo, N.V. (2023). Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities. Biomolecules, 13.","DOI":"10.3390\/biom13040686"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dou, Y., Sun, X., Ma, X., Zhao, X., and Yang, Q. (2021). Intervertebral Disk Degeneration: The Microenvironment and Tissue Engineering Strategies. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.592118"},{"key":"ref_37","first-page":"52","article-title":"Mechanobiology of the Intervertebral Disc and Relevance to Disc Degeneration","volume":"88","author":"Setton","year":"2006","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8884922","DOI":"10.1155\/2021\/8884922","article-title":"Mechanosensitive Ion Channel Piezo1 Activated by Matrix Stiffness Regulates Oxidative Stress-Induced Senescence and Apoptosis in Human Intervertebral Disc Degeneration","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13075-023-03093-9","article-title":"Aberrant Mechanical Loading Induces Annulus Fibrosus Cells Apoptosis in Intervertebral Disc Degeneration via Mechanosensitive Ion Channel Piezo1","volume":"25","author":"Liu","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-022-01259-6","article-title":"Targeting Integrin Pathways: Mechanisms and Advances in Therapy","volume":"8","author":"Pang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"151770","DOI":"10.1016\/j.acthis.2021.151770","article-title":"The Hippo Pathway Orchestrates Cytoskeletal Organisation during Intervertebral Disc Degeneration","volume":"123","author":"Zhang","year":"2021","journal-title":"Acta Histochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1097\/BRS.0b013e318175cae7","article-title":"Dynamic Compression Effects on Intervertebral Disc Mechanics and Biology","volume":"33","author":"Korecki","year":"2008","journal-title":"Spine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/s12964-024-01803-7","article-title":"The Role of miR-155-5p in Inflammation and Mechanical Loading during Intervertebral Disc Degeneration","volume":"22","author":"Cazzanelli","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-023-01501-9","article-title":"Cellular Mechanotransduction in Health and Diseases: From Molecular Mechanism to Therapeutic Targets","volume":"8","author":"Di","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110852","DOI":"10.1016\/j.cellsig.2023.110852","article-title":"Focal Adhesion Kinase (FAK): Its Structure, Characteristics, and Signaling in Skeletal System","volume":"111","author":"Huang","year":"2023","journal-title":"Cell. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/jor.24169","article-title":"Fibronectin Induced ITG\u03b21\/FAK-Dependent Apoptotic Pathways Determines the Fate of Degenerative NP Cells","volume":"37","author":"Wu","year":"2019","journal-title":"J. Orthop. Res."},{"key":"ref_47","first-page":"4751","article-title":"S-Glutathionylation of LMW-PTP Regulates VEGF-Mediated FAK Activation and Endothelial Cell Migration","volume":"125","author":"Abdelsaid","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e70040","DOI":"10.1002\/jsp2.70040","article-title":"Low-Frequency Cyclic Stretch Upregulates the Expression of Nuclear Factor Erythroid 2-Related Factor 2 in Human Nucleus Pulposus Cells to Inhibit the Resistin-Induced Interleukin-20 Expression","volume":"8","author":"Yen","year":"2025","journal-title":"JOR Spine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/j.wneu.2023.05.010","article-title":"N-Acetylserotonin Protects Rat Nucleus Pulposus Cells Against Oxidative Stress Injury by Activating the PI3K\/AKT Signaling Pathway","volume":"176","author":"Yidian","year":"2023","journal-title":"World Neurosurg."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhou, C., Yao, S., Fu, F., Bian, Y., Zhang, Z., Zhang, H., Luo, H., Ge, Y., Chen, Y., and Ji, W. (2022). Morroniside Attenuates Nucleus Pulposus Cell Senescence to Alleviate Intervertebral Disc Degeneration via Inhibiting ROS-Hippo-P53 Pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.942435"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"C728","DOI":"10.1152\/ajpcell.00544.2022","article-title":"The Role of PIEZO Ion Channels in the Musculoskeletal System","volume":"324","author":"Savadipour","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12933-024-02238-7","article-title":"Ion Channel Piezo1 Activation Aggravates the Endothelial Dysfunction under a High Glucose Environment","volume":"23","author":"Zhang","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbrc.2023.02.043","article-title":"Piezo1 Alleviates Acetaminophen-Induced Acute Liver Injury by Activating Nrf2 and Reducing Mitochondrial Reactive Oxygen Species","volume":"652","author":"Wang","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s13577-021-00600-5","article-title":"Piezo1 Mediates Endothelial Atherogenic Inflammatory Responses via Regulation of YAP\/TAZ Activation","volume":"35","author":"Yang","year":"2022","journal-title":"Hum. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102291","DOI":"10.1016\/j.tice.2023.102291","article-title":"Elucidating the Mechanism of IL-1\u03b2-Mediated Piezo1 Expression Regulation of Chondrocyte Autophagy and Apoptosis via the PI3K\/AKT\/mTOR Signaling Pathway","volume":"86","author":"Chen","year":"2024","journal-title":"Tissue Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s10020-021-00360-w","article-title":"G Protein Coupled Estrogen Receptor Attenuates Mechanical Stress-Mediated Apoptosis of Chondrocyte in Osteoarthritis via Suppression of Piezo1","volume":"27","author":"Sun","year":"2021","journal-title":"Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13075-022-02804-y","article-title":"Excessive Mechanical Stress-Induced Intervertebral Disc Degeneration Is Related to Piezo1 Overexpression Triggering the Imbalance of Autophagy\/Apoptosis in Human Nucleus Pulpous","volume":"24","author":"Shi","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E203","DOI":"10.1097\/BRS.0000000000004203","article-title":"Single Impact Injury of Vertebral Endplates Without Structural Disruption, Initiates Disc Degeneration Through Piezo1 Mediated Inflammation and Metabolism Dysfunction","volume":"47","author":"Sun","year":"2022","journal-title":"Spine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"106681","DOI":"10.1016\/j.intimp.2020.106681","article-title":"Piezo1 Activates the NLRP3 Inflammasome in Nucleus Pulposus Cell-Mediated by Ca2+\/NF-\u03baB Pathway","volume":"85","author":"Sun","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.joca.2015.07.019","article-title":"Intermittent Cyclic Mechanical Tension Promotes Endplate Cartilage Degeneration via Canonical Wnt Signaling Pathway and E-Cadherin\/\u03b2-Catenin Complex Cross-Talk","volume":"24","author":"Xu","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"H634","DOI":"10.1152\/ajpheart.00717.2011","article-title":"Activation of Endothelial TRPV4 Channels Mediates Flow-Induced Dilation in Human Coronary Arterioles: Role of Ca2+ Entry and Mitochondrial ROS Signaling","volume":"302","author":"Bubolz","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7283683","DOI":"10.1155\/2019\/7283683","article-title":"Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial Ischemia\/Reperfusion","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cambria, E., Arlt, M.J.E., Wandel, S., Krupkova, O., Hitzl, W., Passini, F.S., Hausmann, O.N., Snedeker, J.G., Ferguson, S.J., and Wuertz-Kozak, K. (2020). TRPV4 Inhibition and CRISPR-Cas9 Knockout Reduce Inflammation Induced by Hyperphysiological Stretching in Human Annulus Fibrosus Cells. Cells, 9.","DOI":"10.3390\/cells9071736"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1149","DOI":"10.1002\/jsp2.1149","article-title":"TRPV4 Mediates Cell Damage Induced by Hyperphysiological Compression and Regulates COX2\/PGE2 in Intervertebral Discs","volume":"4","author":"Cambria","year":"2021","journal-title":"JOR Spine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"194","DOI":"10.22203\/eCM.v041a14","article-title":"Spatiotemporal and Functional Characterisation of Transient Receptor Potential Vanilloid 4 (TRPV4) in the Murine Intervertebral Disc","volume":"41","author":"Kim","year":"2021","journal-title":"Eur. Cell. Mater."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.joca.2024.04.001","article-title":"Transient Receptor Potential Vanilloid 4 Regulates Extracellular Matrix Composition and Mediates Load-Induced Intervertebral Disc Degeneration in a Mouse Model","volume":"32","author":"Lawrence","year":"2024","journal-title":"Osteoarthr. Cartil."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e22714","DOI":"10.1096\/fj.202201388R","article-title":"Modulation of TRPV4 Protects against Degeneration Induced by Sustained Loading and Promotes Matrix Synthesis in the Intervertebral Disc","volume":"37","author":"Easson","year":"2023","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Xu, W., Zheng, H., Fu, Y., Gu, Y., Zou, H., Yuan, Y., Gu, J., Liu, Z., and Bian, J. (2022). Role of PI3K\/Akt-Mediated Nrf2\/HO-1 Signaling Pathway in Resveratrol Alleviation of Zearalenone-Induced Oxidative Stress and Apoptosis in TM4 Cells. Toxins, 14.","DOI":"10.3390\/toxins14110733"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"57870","DOI":"10.18632\/oncotarget.18628","article-title":"The PI3K\/Akt Pathway: A Critical Player in Intervertebral Disc Degeneration","volume":"8","author":"Ouyang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/mTOR Signaling Pathway in Osteoarthritis: A Narrative Review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112101","DOI":"10.1016\/j.intimp.2024.112101","article-title":"Genkwanin Alleviates Intervertebral Disc Degeneration via Regulating ITGA2\/PI3K\/AKT Pathway and Inhibiting Apoptosis and Senescence","volume":"133","author":"Li","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6699326","DOI":"10.1155\/2021\/6699326","article-title":"Cyclic Mechanical Stretch Ameliorates the Degeneration of Nucleus Pulposus Cells through Promoting the ITGA2\/PI3K\/AKT Signaling Pathway","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"E248","DOI":"10.1097\/BRS.0000000000001220","article-title":"Low Intensity Pulsed Ultrasound Promotes the Extracellular Matrix Synthesis of Degenerative Human Nucleus Pulposus Cells Through FAK\/PI3K\/Akt Pathway","volume":"41","author":"Zhang","year":"2016","journal-title":"Spine"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Huang, C., Gan, D., Luo, F., Wan, S., Chen, J., Wang, A., Li, B., and Zhu, X. (2019). Interaction Mechanisms Between the NOX4\/ROS and RhoA\/ROCK1 Signaling Pathways as New Anti- Fibrosis Targets of Ursolic Acid in Hepatic Stellate Cells. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00431"},{"key":"ref_76","first-page":"5324","article-title":"RhoA\/ROCK Pathway: Implication in Osteoarthritis and Therapeutic Targets","volume":"11","author":"Deng","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ning, L., Gao, L., Zhang, F., Li, X., and Wang, T. (2021). Mechanical Stretch Induces Annulus Fibrosus Cell Senescence through Activation of the RhoA\/ROCK Pathway. Biomed Res. Int., 2021.","DOI":"10.1155\/2021\/5321121"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ko, E., Kim, D., Min, D.W., Kwon, S.-H., and Lee, J.-Y. (2021). Nrf2 Regulates Cell Motility through RhoA-ROCK1 Signalling in Non-Small-Cell Lung Cancer Cells. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81021-0"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.2147\/JIR.S431026","article-title":"Leptin Induces MMP-1 Expression Through the RhoA\/ERK1\/2\/NF-\u03baB Axis in Human Intervertebral Disc Cartilage Endplate-Derived Stem Cells","volume":"16","author":"Hua","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jbiosc.2013.10.018","article-title":"Role of P38, ERK1\/2, Focal Adhesion Kinase, RhoA\/ROCK and Cytoskeleton in the Adipogenesis of Human Mesenchymal Stem Cells","volume":"117","author":"Xu","year":"2014","journal-title":"J. Biosci. Bioeng."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e23832","DOI":"10.1096\/fj.202400848R","article-title":"A Role for YAP\/FOXM1\/Nrf2 Axis in Oxidative Stress and Apoptosis of Cataract Induced by UVB Irradiation","volume":"38","author":"Hong","year":"2024","journal-title":"FASEB J."},{"key":"ref_82","unstructured":"Preedy, V.R., and Patel, V.B. (2021). Chapter 15\u2014Nrf2, YAP, Antioxidant Potential, and Cancer. Cancer, Academic Press. [2nd ed.]."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"102427","DOI":"10.1016\/j.isci.2021.102427","article-title":"Myeloid Nrf2 Deficiency Aggravates Non-Alcoholic Steatohepatitis Progression by Regulating YAP-Mediated NLRP3 Inflammasome Signaling","volume":"24","author":"Wang","year":"2021","journal-title":"iScience"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s13287-024-04011-9","article-title":"Emerging Role and Function of Hippo-YAP\/TAZ Signaling Pathway in Musculoskeletal Disorders","volume":"15","author":"Han","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zheng-wei, S., Yuan, T., Chao-shuai, F., Lei, Z., Zong-rang, S., Tuan-jiang, L., and Ding-jun, H. (2023). Roles of Hippo\u2013YAP\/TAZ Signalling in Intervertebral Disc Degeneration. Biomed. Pharmacother., 159.","DOI":"10.1016\/j.biopha.2022.114099"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5626487","DOI":"10.1155\/2021\/5626487","article-title":"Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP\/TAZ Pathway","volume":"2021","author":"Wang","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Croft, A.S., Roth, Y., Oswald, K.A.C., \u0106orluka, S., Bermudez-Lekerika, P., and Gantenbein, B. (2021). In Situ Cell Signalling of the Hippo-YAP\/TAZ Pathway in Reaction to Complex Dynamic Loading in an Intervertebral Disc Organ Culture. Int. J. Mol., 22.","DOI":"10.3390\/ijms222413641"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/emboj\/18.5.1321","article-title":"Regulation of JNK Signaling by GSTp","volume":"18","author":"Adler","year":"1999","journal-title":"EMBO J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2147\/DDDT.S392535","article-title":"Andrographolide Inhibits Static Mechanical Pressure-Induced Intervertebral Disc Degeneration via the MAPK\/Nrf2\/HO-1 Pathway","volume":"17","author":"Zhang","year":"2023","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1017\/anr.2024.2","article-title":"Roles of MAPK and Nrf2 Signaling Pathways in Quercetin Alleviating Redox Imbalance Induced by Hydrogen Peroxide in Mammary Epithelial Cells","volume":"1","author":"Li","year":"2024","journal-title":"Anim. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ijsu.2015.08.016","article-title":"Inhibition of Reactive Oxygen Species Downregulates the MAPK Pathway in Rat Spinal Cord after Limb Ischemia Reperfusion Injury","volume":"22","author":"Choi","year":"2015","journal-title":"Int. J. Surg."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhang, H.-J., Liao, H.-Y., Bai, D.-Y., Wang, Z.-Q., and Xie, X.-W. (2021). MAPK \/ERK Signaling Pathway: A Potential Target for the Treatment of Intervertebral Disc Degeneration. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112170"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.joca.2015.11.022","article-title":"Cyclic Tensile Stress of Human Annulus Fibrosus Cells Induces MAPK Activation: Involvement in Proinflammatory Gene Expression","volume":"24","author":"Pratsinis","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s13075-017-1384-z","article-title":"High-Magnitude Compression Accelerates the Premature Senescence of Nucleus Pulposus Cells via the P38 MAPK-ROS Pathway","volume":"19","author":"Li","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"113230","DOI":"10.1016\/j.yexcr.2022.113230","article-title":"Nucleus Pulposus Cell Senescence Is Regulated by Substrate Stiffness and Is Alleviated by LOX Possibly through the Integrin \u03921-P38 MAPK Signaling Pathway","volume":"417","author":"Zhao","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Krupkova, O., Sadowska, A., Kameda, T., Hitzl, W., Hausmann, O.N., Klasen, J., and Wuertz-Kozak, K. (2018). P38 MAPK Facilitates Crosstalk Between Endoplasmic Reticulum Stress and IL-6 Release in the Intervertebral Disc. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01706"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"152667","DOI":"10.1016\/j.scitotenv.2021.152667","article-title":"Content of Toxic Components of Cigarette, Cigarette Smoke vs Cigarette Butts: A Comprehensive Systematic Review","volume":"813","author":"Soleimani","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"106785","DOI":"10.1016\/j.ecss.2020.106785","article-title":"Impact of Cigarette Butts on Microbial Diversity and Dissolved Trace Metals in Coastal Marine Sediment","volume":"240","author":"Chifflet","year":"2020","journal-title":"Estuar. Coast. Shelf Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00175479","article-title":"Oxygen-Dissociation Kinetics in the Blood of Smokers and Non-Smokers: Interaction between Oxygen and Carbon Monoxide at the Hemoglobin Molecule","volume":"345","author":"Rietbrock","year":"1992","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1016\/j.ymthe.2023.06.010","article-title":"Smoking and Tetramer Tryptase Accelerate Intervertebral Disc Degeneration by Inducing METTL14-Mediated DIXDC1 M6 Modification","volume":"31","author":"Tu","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jcm.2017.11.006","article-title":"Intervertebral Disk Nutrients and Transport Mechanisms in Relation to Disk Degeneration: A Narrative Literature Review","volume":"17","year":"2018","journal-title":"J. Chiropr. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1097\/01.brs.0000146499.97948.52","article-title":"Nutrition of the Intervertebral Disc","volume":"29","author":"Urban","year":"2004","journal-title":"Spine"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1002\/jbmr.4009","article-title":"Intervertebral Disc Degeneration Is Associated With Aberrant Endplate Remodeling and Reduced Small Molecule Transport","volume":"35","author":"Ashinsky","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Rodgman, A., and Perfetti, T.A. (2008). The Chemical Components of Tobacco and Tobacco Smoke, CRC Press. [1st ed.].","DOI":"10.1201\/9781420078848"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"108365","DOI":"10.1016\/j.mrrev.2021.108365","article-title":"Relationships among Smoking, Oxidative Stress, Inflammation, Macromolecular Damage, and Cancer","volume":"787","author":"Caliri","year":"2021","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0891-5849(90)90075-T","article-title":"A Comparison of the Free Radical Chemistry of Tobacco-Burning Cigarettes and Cigarettes That Only Heat Tobacco","volume":"8","author":"Pryor","year":"1990","journal-title":"Free Radic. Biol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0891-5849(94)00236-D","article-title":"Detection of Free Radicals in Aqueous Extracts of Cigarette Tar by Electron Spin Resonance","volume":"19","author":"Zang","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.tox.2011.11.014","article-title":"Cigarette Smoke Induces P-Benzoquinone\u2013Albumin Adduct in Blood Serum: Implications on Structure and Ligand Binding Properties","volume":"292","author":"Ghosh","year":"2012","journal-title":"Toxicology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1007\/s13361-018-2011-1","article-title":"Conjugation of Para-Benzoquinone of Cigarette Smoke with Human Hemoglobin Leads to Unstable Tetramer and Reduced Cooperative Oxygen Binding","volume":"29","author":"Mitra","year":"2018","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1476-9255-5-21","article-title":"Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Lung Damage and Prevention by Vitamin C","volume":"5","author":"Banerjee","year":"2008","journal-title":"J. Inflamm."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.bbagen.2019.06.010","article-title":"Iron Homeostasis and Iron-Regulated ROS in Cell Death, Senescence and Human Diseases","volume":"1863","author":"Nakamura","year":"2019","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.freeradbiomed.2022.08.018","article-title":"Iron Overload Promotes Intervertebral Disc Degeneration via Inducing Oxidative Stress and Ferroptosis in Endplate Chondrocytes","volume":"190","author":"Wang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.freeradbiomed.2024.12.043","article-title":"GLS1-Mediated Glutamine Metabolism Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Senescence in Nucleus Pulposus Cells by Modulating Fe2+ Homeostasis","volume":"228","author":"Wu","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.tiv.2016.10.013","article-title":"NADPH Oxidase (NOX) 1 Mediates Cigarette Smoke-Induced Superoxide Generation in Rat Vascular Smooth Muscle Cells","volume":"38","author":"Chang","year":"2017","journal-title":"Toxicol. Vitro"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Wang, X., Murugesan, P., Zhang, P., Xu, S., Peng, L., Wang, C., and Cai, H. (2022). NADPH Oxidase Isoforms in COPD Patients and Acute Cigarette Smoke-Exposed Mice: Induction of Oxidative Stress and Lung Inflammation. Antioxidants, 11.","DOI":"10.3390\/antiox11081539"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.freeradbiomed.2010.02.026","article-title":"Cigarette Smoke Particle-Phase Extract Induces HO-1 Expression in Human Tracheal Smooth Muscle Cells: Role of the c-Src\/NADPH Oxidase\/MAPK\/Nrf2 Signaling Pathway","volume":"48","author":"Cheng","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/jcp.22270","article-title":"Cigarette Smoke Extract Induces HO-1 Expression in Mouse Cerebral Vascular Endothelial Cells: Involvement of c-Src\/NADPH Oxidase\/PDGFR\/JAK2\/STAT3 Pathway","volume":"225","author":"Shih","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.toxlet.2019.09.022","article-title":"Mitochondrial Dysfunction Is Associated with Miro1 Reduction in Lung Epithelial Cells by Cigarette Smoke","volume":"317","author":"Sundar","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_119","first-page":"271","article-title":"A Comparison of Toxicity Mechanisms of Cigarette Smoke on Isolated Mitochondria Obtained from Rat Liver and Skin","volume":"14","author":"Naserzadeh","year":"2015","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_120","first-page":"129","article-title":"Short- and Long-Term Effects of Cigarette Smoke Exposure on Glutathione Homeostasis in Human Bronchial Epithelial Cells","volume":"32","author":"Bazzini","year":"2013","journal-title":"Cell Physiol."},{"key":"ref_121","first-page":"BC19","article-title":"Effect of Cigarette Smoking on Selected Antioxidant Enzymes and Oxidative Stress Biomarkers","volume":"14","author":"Joshi","year":"2020","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cmet.2005.05.001","article-title":"Mitochondrial Complex III Is Required for Hypoxia-Induced ROS Production and Cellular Oxygen Sensing","volume":"1","author":"Guzy","year":"2005","journal-title":"Cell Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.redox.2017.04.025","article-title":"Mitochondrial Complex I Deactivation Is Related to Superoxide Production in Acute Hypoxia","volume":"12","author":"Ramos","year":"2017","journal-title":"Redox Biol."},{"key":"ref_124","first-page":"5447","article-title":"A Nuclear Factor Induced by Hypoxia via de Novo Protein Synthesis Binds to the Human Erythropoietin Gene Enhancer at a Site Required for Transcriptional Activation","volume":"12","author":"Semenza","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zhang, L., Ludden, C.M., Cullen, A.J., Tew, K.D., Branco de Barros, A.L., and Townsend, D.M. (2023). Nuclear Factor Kappa B Expression in Non-Small Cell Lung Cancer. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115459"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.biopha.2014.08.007","article-title":"N-Acetyl-L-Cysteine Sensitizes Pancreatic Cancers to Gemcitabine by Targeting the NF\u03baB Pathway","volume":"68","author":"Qanungo","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"25130","DOI":"10.1074\/jbc.M001914200","article-title":"Reactive Oxygen Species Generated at Mitochondrial Complex III Stabilize Hypoxia-Inducible Factor-1\u03b1 during Hypoxia","volume":"275","author":"Chandel","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_128","unstructured":"and Singh, J. (FEBS J., 2025). Redox Imbalance and Hypoxia-Inducible Factors: A Multifaceted Crosstalk, FEBS J., early view."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1038\/s41467-022-30169-y","article-title":"A Reversible Mitochondrial Complex I Thiol Switch Mediates Hypoxic Avoidance Behavior in C. Elegans","volume":"13","author":"Onukwufor","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-1-4419-9280-2_21","article-title":"Mitochondrial Complex II Is Essential for Hypoxia-Induced ROS Generation and Vasoconstriction in the Pulmonary Vasculature","volume":"Volume 536","author":"Pequignot","year":"2003","journal-title":"Chemoreception"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1165\/ajrcmb.15.5.8918370","article-title":"Pulmonary Artery NADPH-Oxidase Is Activated in Hypoxic Pulmonary Vasoconstriction","volume":"15","author":"Marshall","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_132","first-page":"134","article-title":"Knockdown of Hypoxia-Inducible Factor-1 Alpha Reduces Proliferation, Induces Apoptosis and Attenuates the Aggressive Phenotype of Retinoblastoma WERI-Rb-1 Cells under Hypoxic Conditions","volume":"44","author":"Xia","year":"2014","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Averill-Bates, D. (2024). Reactive Oxygen Species and Cell Signaling. Review. Biochim. Biophys. Acta Mol. Cell Res., 1871.","DOI":"10.1016\/j.bbamcr.2023.119573"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1089\/ars.2019.7935","article-title":"Targeting Hypoxia-Inducible Factor-1-Mediated Metastasis for Cancer Therapy","volume":"34","author":"Ma","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1007\/s00125-024-06185-6","article-title":"Activation of the Hypoxia-Inducible Factor Pathway by Roxadustat Improves Glucose Metabolism in Human Primary Myotubes from Men","volume":"67","author":"Sree","year":"2024","journal-title":"Diabetologia"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2024.08.016","article-title":"Hypoxia Decreases Mitochondrial ROS Production in Cells","volume":"224","author":"Sen","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cbi.2017.01.001","article-title":"Low Glucose Stress Decreases Cellular NADH and Mitochondrial ATP in Colonic Epithelial Cancer Cells: Influence of Mitochondrial Substrates","volume":"264","author":"Circu","year":"2017","journal-title":"Chem.-Biol. Interact."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.freeradbiomed.2019.09.020","article-title":"Glucose Starvation-Induced Oxidative Stress Causes Mitochondrial Dysfunction and Apoptosis via Prohibitin 1 Upregulation in Human Breast Cancer Cells","volume":"145","author":"Raut","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cellsig.2012.09.020","article-title":"Starvation-Induced Autophagy Is Regulated by Mitochondrial Reactive Oxygen Species Leading to AMPK Activation","volume":"25","author":"Li","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Owada, S., Shimoda, Y., Tsuchihara, K., and Esumi, H. (2013). Critical Role of H2O2 Generated by NOX4 during Cellular Response under Glucose Deprivation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056628"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature11066","article-title":"AMPK Regulates NADPH Homeostasis to Promote Tumour Cell Survival during Energy Stress","volume":"485","author":"Jeon","year":"2012","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Ren, Y., and Shen, H.-M. (2019). Critical Role of AMPK in Redox Regulation under Glucose Starvation. Redox Biol., 25.","DOI":"10.1016\/j.redox.2019.101154"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"6666","DOI":"10.1002\/jcp.30329","article-title":"Glucose Deprivation-Induced Endoplasmic Reticulum Stress Response Plays a Pivotal Role in Enhancement of TRAIL Cytotoxicity","volume":"236","author":"Kalimuthu","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1161\/CIRCRESAHA.113.301787","article-title":"Activation of NADPH Oxidase 4 in the Endoplasmic Reticulum Promotes Cardiomyocyte Autophagy and Survival During Energy Stress Through the Protein Kinase RNA-Activated-Like Endoplasmic Reticulum Kinase\/Eukaryotic Initiation Factor 2\u03b1\/Activating Transcription Factor 4 Pathway","volume":"113","author":"Sciarretta","year":"2013","journal-title":"Circ. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.molcel.2018.01.001","article-title":"Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation","volume":"69","author":"Li","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Iliadis, S., and Papanikolaou, N.A. (2024). Reactive Oxygen Species Mechanisms That Regulate Protein\u2013Protein Interactions in Cancer. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202408.1413.v1"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1080\/15548627.2020.1822097","article-title":"Mitophagy in Degenerative Joint Diseases","volume":"17","author":"Sun","year":"2021","journal-title":"Autophagy"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"5601593","DOI":"10.1155\/2017\/5601593","article-title":"ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration","volume":"2017","author":"Feng","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The Endoplasmic Reticulum: Structure, Function and Response to Cellular Signaling","volume":"73","author":"Schwarz","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"110986","DOI":"10.1016\/j.cellsig.2023.110986","article-title":"The Role of Endoplasmic Reticulum Stress, Mitochondrial Dysfunction and Their Crosstalk in Intervertebral Disc Degeneration","volume":"114","author":"Yao","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"107525","DOI":"10.1016\/j.pharmthera.2020.107525","article-title":"Role of the ERO1-PDI Interaction in Oxidative Protein Folding and Disease","volume":"210","author":"Shergalis","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal Integration in the Endoplasmic Reticulum Unfolded Protein Response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/ars.2014.5851","article-title":"Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease","volume":"21","author":"Cao","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.molcel.2010.11.010","article-title":"Oxidative Protein Folding by an Endoplasmic Reticulum-Localized Peroxiredoxin","volume":"40","author":"Zito","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1242\/jcs.067843","article-title":"Peroxiredoxin IV Protects Cells from Oxidative Stress by Removing H2O2 Produced during Disulphide Formation","volume":"123","author":"Tavender","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"65","DOI":"10.14348\/molcells.2016.2349","article-title":"The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction","volume":"39","author":"Netto","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.freeradbiomed.2015.02.019","article-title":"The Antioxidant Machinery of the Endoplasmic Reticulum: Protection and Signaling","volume":"83","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1089\/ars.2021.0135","article-title":"Nox, Nox, Are You There? The Role of NADPH Oxidases in the Peripheral Nervous System","volume":"37","author":"Eid","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1128\/MCB.01445-09","article-title":"Nox4-Derived H2O2 Mediates Endoplasmic Reticulum Signaling through Local Ras Activation","volume":"30","author":"Wu","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.molcel.2016.05.040","article-title":"Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface","volume":"63","author":"Booth","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"8170","DOI":"10.1074\/jbc.M113.504159","article-title":"Isoform- and Species-Specific Control of Inositol 1,4,5-Trisphosphate (IP3) Receptors by Reactive Oxygen Species","volume":"289","author":"Madesh","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ceca.2017.05.003","article-title":"Mitochondrial and Endoplasmic Reticulum Calcium Homeostasis and Cell Death","volume":"69","author":"Marchi","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s12276-021-00560-8","article-title":"The Aftermath of the Interplay between the Endoplasmic Reticulum Stress Response and Redox Signaling","volume":"53","author":"Bhattarai","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_164","first-page":"3649","article-title":"Redox Controls UPR to Control Redox","volume":"127","author":"Eletto","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"173749","DOI":"10.1016\/j.ejphar.2020.173749","article-title":"Crosstalk between Endoplasmic Reticulum Stress and Oxidative Stress: Focus on Protein Disulfide Isomerase and Endoplasmic Reticulum Oxidase 1","volume":"892","author":"Victor","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Gardner, B.M., Pincus, D., Gotthardt, K., Gallagher, C.M., and Walter, P. (2013). Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a013169"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/cdd.2014.90","article-title":"Pro-Apoptotic BIM Is an Essential Initiator of Physiological Endothelial Cell Death Independent of Regulation by FOXO3","volume":"21","author":"Koenig","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/ars.2013.5262","article-title":"Endoplasmic Reticulum Stress and Nox-Mediated Reactive Oxygen Species Signaling in the Peripheral Vasculature: Potential Role in Hypertension","volume":"20","author":"Santos","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Chaube, R., and Werstuck, G.H. (2016). Mitochondrial ROS versus ER ROS: Which Comes First in Myocardial Calcium Dysregulation?. Front. Cardiovasc. Med., 3.","DOI":"10.3389\/fcvm.2016.00036"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.coph.2009.11.008","article-title":"Targeting the Redox Regulation of SERCA in Vascular Physiology and Disease","volume":"10","author":"Tong","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Huang, J., Zhou, Q., Ren, Q., Luo, L., Ji, G., and Zheng, T. (2023). Endoplasmic Reticulum Stress Associates with the Development of Intervertebral Disc Degeneration. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1094394"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/term.1866","article-title":"Treatment of the Degenerated Intervertebral Disc; Closure, Repair and Regeneration of the Annulus Fibrosus","volume":"9","author":"Sharifi","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1097\/01.brs.0000222019.84095.23","article-title":"Cervical Intervertebral Disc Degeneration Induced by Unbalanced Dynamic and Static Forces: A Novel In Vivo Rat Model","volume":"31","author":"Wang","year":"2006","journal-title":"Spine"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Kang, H., Dong, Y., Peng, R., Liu, H., Guo, Q., Song, K., Zhu, M., Yu, K., Wu, W., and Li, F. (2022). Inhibition of IRE1 Suppresses the Catabolic Effect of IL-1\u03b2 on Nucleus Pulposus Cell and Prevents Intervertebral Disc Degeneration In Vivo. Biochem Pharmacol., 197.","DOI":"10.1016\/j.bcp.2022.114932"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s10495-011-0596-y","article-title":"Lentiviral shRNA Silencing of CHOP Inhibits Apoptosis Induced by Cyclic Stretch in Rat Annular Cells and Attenuates Disc Degeneration in the Rats","volume":"16","author":"Zhang","year":"2011","journal-title":"Apoptosis"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"8810698","DOI":"10.1155\/2021\/8810698","article-title":"Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER-Mitochondrial Ca2+ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression","volume":"2021","author":"Lin","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.archger.2014.07.002","article-title":"Oxidative Stress Participates in Age-Related Changes in Rat Lumbar Intervertebral Discs","volume":"59","author":"Hou","year":"2014","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/bj2810419","article-title":"Production of Hydroxyl Radicals from the Simultaneous Generation of Superoxide and Nitric Oxide","volume":"281","author":"Hogg","year":"1992","journal-title":"Biochem. J."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1097\/BRS.0b013e31819f2330","article-title":"Peroxynitrite Induces Gene Expression in Intervertebral Disc Cells","volume":"34","author":"Poveda","year":"2009","journal-title":"Spine"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s13075-015-0834-8","article-title":"Excessive Reactive Oxygen Species Are Therapeutic Targets for Intervertebral Disc Degeneration","volume":"17","author":"Suzuki","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1083\/jcb.200608073","article-title":"Chaperone-Mediated Coupling of Endoplasmic Reticulum and Mitochondrial Ca2+ Channels","volume":"175","author":"Szabadkai","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/jor.22320","article-title":"Mitochondrial-Derived Reactive Oxygen Species (ROS) Play a Causal Role in Aging-Related Intervertebral Disc Degeneration","volume":"31","author":"Nasto","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1042\/BST20230012","article-title":"Beyond the TCA Cycle: New Insights into Mitochondrial Calcium Regulation of Oxidative Phosphorylation","volume":"51","author":"Lee","year":"2023","journal-title":"Biochem. Soc. Trans."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA Cycle Metabolites Control Physiology and Disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.molcel.2012.09.025","article-title":"Physiological Roles of Mitochondrial Reactive Oxygen Species","volume":"48","author":"Sena","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nchembio.607","article-title":"Chemistry and Biology of Reactive Oxygen Species in Signaling or Stress Responses","volume":"7","author":"Dickinson","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"49064","DOI":"10.1074\/jbc.M407715200","article-title":"Complex III Releases Superoxide to Both Sides of the Inner Mitochondrial Membrane","volume":"279","author":"Muller","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41420-022-01212-0","article-title":"GPX4-Independent Ferroptosis\u2014A New Strategy in Disease\u2019s Therapy","volume":"8","author":"Ma","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1158\/0008-5472.CAN-06-0484","article-title":"A Novel Role for Human Sulfiredoxin in the Reversal of Glutathionylation","volume":"66","author":"Findlay","year":"2006","journal-title":"Cancer Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"4877","DOI":"10.1038\/onc.2008.132","article-title":"Protein Cysteine Sulfinic Acid Reductase (Sulfiredoxin) as a Regulator of Cell Proliferation and Drug Response","volume":"27","author":"Lei","year":"2008","journal-title":"Oncogene"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Lyamzaev, K.G., Panteleeva, A.A., Simonyan, R.A., Avetisyan, A.V., and Chernyak, B.V. (2023). Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis. Cells, 12.","DOI":"10.3390\/cells12040611"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"5080843","DOI":"10.1155\/2019\/5080843","article-title":"Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis","volume":"2019","author":"Su","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/acel.12650","article-title":"The Path from Mitochondrial ROS to Aging Runs through the Mitochondrial Permeability Transition Pore","volume":"16","author":"Rottenberg","year":"2017","journal-title":"Aging Cell"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10495-012-0708-3","article-title":"Role of Mitochondrial Pathway in Compression-Induced Apoptosis of Nucleus Pulposus Cells","volume":"17","author":"Ding","year":"2012","journal-title":"Apoptosis"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1159\/000366330","article-title":"The Responses of Autophagy and Apoptosis to Oxidative Stress in Nucleus Pulposus Cells: Implications for Disc Degeneration","volume":"34","author":"Chen","year":"2014","journal-title":"Cell Physiol. Biochem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1007\/s00586-014-3630-2","article-title":"Pyrroloquinoline Quinone Protects Nucleus Pulposus Cells from Hydrogen Peroxide-Induced Apoptosis by Inhibiting the Mitochondria-Mediated Pathway","volume":"24","author":"Yang","year":"2015","journal-title":"Eur. Spine J."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/s41419-018-1024-9","article-title":"Parkin-Mediated Mitophagy as a Potential Therapeutic Target for Intervertebral Disc Degeneration","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10495-018-1455-x","article-title":"Critical Contribution of RIPK1 Mediated Mitochondrial Dysfunction and Oxidative Stress to Compression-Induced Rat Nucleus Pulposus Cells Necroptosis and Apoptosis","volume":"23","author":"Chen","year":"2018","journal-title":"Apoptosis"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2018.05.014","article-title":"CsA Attenuates Compression-Induced Nucleus Pulposus Mesenchymal Stem Cells Apoptosis via Alleviating Mitochondrial Dysfunction and Oxidative Stress","volume":"205","author":"Li","year":"2018","journal-title":"Life Sci."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41420-023-01353-w","article-title":"Synergistic Mechanism between the Endoplasmic Reticulum and Mitochondria and Their Crosstalk with Other Organelles","volume":"9","author":"Zhang","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1021\/acs.chemrestox.8b00379","article-title":"Working Together: Redox Signaling between the Endoplasmic Reticulum and Mitochondria","volume":"32","author":"Siegenthaler","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","article-title":"Mitochondrial Dynamics in Health and Disease: Mechanisms and Potential Targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Xu, H., Guan, N., Ren, Y.-L., Wei, Q.-J., Tao, Y.-H., Yang, G.-S., Liu, X.-Y., Bu, D.-F., Zhang, Y., and Zhu, S.-N. (2018). IP3R-Grp75-VDAC1-MCU Calcium Regulation Axis Antagonists Protect Podocytes from Apoptosis and Decrease Proteinuria in an Adriamycin Nephropathy Rat Model. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-0940-3"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.molcel.2009.09.030","article-title":"Stepwise Activation of BAX and BAK by tBID, BIM, and PUMA Initiates Mitochondrial Apoptosis","volume":"36","author":"Kim","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11357-009-9121-4","article-title":"Both Endoplasmic Reticulum and Mitochondria Are Involved in Disc Cell Apoptosis and Intervertebral Disc Degeneration in Rats","volume":"32","author":"Zhao","year":"2010","journal-title":"Age"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cca.2007.01.028","article-title":"Malondialdehyde as Biomarker of Oxidative Damage to Lipids Caused by Smoking","volume":"380","author":"Lykkesfeldt","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1165\/ajrcmb.19.6.3130","article-title":"Smoking-Associated Mitochondrial DNA Mutations and Lipid Peroxidation in Human Lung Tissues","volume":"19","author":"Fahn","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"6685043","DOI":"10.1155\/2020\/6685043","article-title":"Allicin Attenuated Advanced Oxidation Protein Product-Induced Oxidative Stress and Mitochondrial Apoptosis in Human Nucleus Pulposus Cells","volume":"2020","author":"Xiang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/00207454.2019.1667790","article-title":"Acute-Phase Serum Superoxide Dismutase Level as a Predictive Biomarker for Stroke-Associated Infection","volume":"130","author":"Lin","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e1280","DOI":"10.1002\/jsp2.1280","article-title":"Biomarkers for Intervertebral Disc and Associated Back Pain: From Diagnosis to Disease Prognosis and Personalized Treatment","volume":"6","author":"Grad","year":"2023","journal-title":"JOR Spine"},{"key":"ref_211","first-page":"RP106040","article-title":"In Vivo Autofluorescence Lifetime Imaging of the Drosophila Brain Captures Metabolic Shifts Associated with Memory Formation","volume":"14","author":"Roussel","year":"2025","journal-title":"eLife"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"105","DOI":"10.18383\/j.tom.2015.00175","article-title":"Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients","volume":"1","author":"Xu","year":"2015","journal-title":"Tomography"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.biotechadv.2013.07.010","article-title":"Tissue Engineering Strategies Applied in the Regeneration of the Human Intervertebral Disk","volume":"31","author":"Correia","year":"2013","journal-title":"Biotechnol. Adv."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.spinee.2010.04.017","article-title":"Analysis of the Incidence and Clinical Effect of the Heterotopic Ossification in a Single-Level Cervical Artificial Disc Replacement","volume":"10","author":"Lee","year":"2010","journal-title":"Spine J."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.intimp.2018.09.019","article-title":"Naringin Protects against Perfluorooctane Sulfonate-Induced Liver Injury by Modulating NRF2 and NF-\u03baB in Mice","volume":"65","author":"Lv","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1080\/03008207.2019.1631299","article-title":"Naringin Alleviates H2O2-Induced Apoptosis via the PI3K\/Akt Pathway in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells","volume":"61","author":"Nan","year":"2020","journal-title":"Connect. Tissue Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"7031397","DOI":"10.1155\/2016\/7031397","article-title":"The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress","volume":"2016","author":"Krupkova","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/stem.3322","article-title":"Cartilage Endplate Stem Cells Inhibit Intervertebral Disc Degeneration by Releasing Exosomes to Nucleus Pulposus Cells to Activate Akt\/Autophagy","volume":"39","author":"Luo","year":"2021","journal-title":"Stem Cells"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/978-1-60761-756-3_22","article-title":"Rescue of Misfolded Proteins and Stabilization by Small Molecules","volume":"648","author":"Stevens","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biocel.2015.01.015","article-title":"The Therapeutic Effects of 4-Phenylbutyric Acid in Maintaining Proteostasis","volume":"61","author":"Kolb","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"6492879","DOI":"10.1155\/2021\/6492879","article-title":"The Role of Unfolded Protein Response in Human Intervertebral Disc Degeneration: Perk and IRE1-\u03b1 as Two Potential Therapeutic Targets","volume":"2021","author":"Wen","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.lfs.2019.04.064","article-title":"Berberine Ameliorates Oxidative Stress-Induced Apoptosis by Modulating ER Stress and Autophagy in Human Nucleus Pulposus Cells","volume":"228","author":"Luo","year":"2019","journal-title":"Life Sci."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"6719460","DOI":"10.1155\/2018\/6719460","article-title":"Tauroursodeoxycholic Acid Protects Nucleus Pulposus Cells from Compression-Induced Apoptosis and Necroptosis via Inhibiting Endoplasmic Reticulum Stress","volume":"2018","author":"Wang","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/jor.23787","article-title":"The Unfolded Protein Response Mediated by PERK Is Casually Related to the Pathogenesis of Intervertebral Disc Degeneration","volume":"36","author":"Fujii","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.freeradbiomed.2009.10.039","article-title":"Consequences of Long-Term Oral Administration of the Mitochondria-Targeted Antioxidant MitoQ to Wild-Type Mice","volume":"48","author":"Logan","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"e12779","DOI":"10.1111\/cpr.12779","article-title":"The Mitochondria-Targeted Anti-Oxidant MitoQ Protects against Intervertebral Disc Degeneration by Ameliorating Mitochondrial Dysfunction and Redox Imbalance","volume":"53","author":"Kang","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"101394","DOI":"10.1016\/j.arr.2021.101394","article-title":"The Potential Role of Melatonin in Retarding Intervertebral Disc Ageing and Degeneration: A Systematic Review","volume":"70","author":"Cheng","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.joca.2020.05.011","article-title":"Melatonin Activates Autophagy via the NF-\u03baB Signaling Pathway to Prevent Extracellular Matrix Degeneration in Intervertebral Disc","volume":"28","author":"Chen","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/jcmm.13903","article-title":"Melatonin Protects Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the Sirt1-autophagy Pathway","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1111\/jcmm.14125","article-title":"Melatonin Ameliorates Intervertebral Disc Degeneration via the Potential Mechanisms of Mitophagy Induction and Apoptosis Inhibition","volume":"23","author":"Chen","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"e1003","DOI":"10.1002\/jsp2.1003","article-title":"The Potential of CRISPR\/Cas9 Genome Editing for the Study and Treatment of Intervertebral Disc Pathologies","volume":"1","author":"Krupkova","year":"2018","journal-title":"JOR Spine"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1080\/15548627.2021.1872227","article-title":"HIF1A Alleviates Compression-Induced Apoptosis of Nucleus Pulposus Derived Stem Cells via Upregulating Autophagy","volume":"17","author":"He","year":"2021","journal-title":"Autophagy"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2019.07.026","article-title":"Mesenchymal Stem Cell-Derived Exosomes Ameliorate Intervertebral Disc Degeneration via Anti-Oxidant and Anti-Inflammatory Effects","volume":"143","author":"Xia","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0753-3322(03)00043-X","article-title":"The Importance of Glutathione in Human Disease","volume":"57","author":"Townsend","year":"2003","journal-title":"Biomed. Pharmacother."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"4482642","DOI":"10.1155\/2024\/4482642","article-title":"Glutathione: A Key Regulator of Extracellular Matrix and Cell Death in Intervertebral Disc Degeneration","volume":"2024","author":"Li","year":"2024","journal-title":"Mediat. Inflamm."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3109\/03008207.2013.876421","article-title":"Glutathione Protects Human Nucleus Pulposus Cells from Cell Apoptosis and Inhibition of Matrix Synthesis","volume":"55","author":"Yang","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.joca.2013.10.002","article-title":"Autophagy Is Activated in Compression-Induced Cell Degeneration and Is Mediated by Reactive Oxygen Species in Nucleus Pulposus Cells Exposed to Compression","volume":"21","author":"Ma","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.bbrc.2017.03.111","article-title":"Oxidative Damage Induces Apoptosis and Promotes Calcification in Disc Cartilage Endplate Cell through ROS\/MAPK\/NF-\u03baB Pathway: Implications for Disc Degeneration","volume":"516","author":"Han","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Gao, J., Wang, Y., Folta, K.M., Krishna, V., Bai, W., Indeglia, P., Georgieva, A., Nakamura, H., Koopman, B., and Moudgil, B. (2011). Polyhydroxy Fullerenes (Fullerols or Fullerenols): Beneficial Effects on Growth and Lifespan in Diverse Biological Models. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019976"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.spinee.2013.04.004","article-title":"Fullerol Nanoparticles Suppress Inflammatory Response and Adipogenesis of Vertebral Bone Marrow Stromal Cells\u2014A Potential Novel Treatment for Intervertebral Disc Degeneration","volume":"13","author":"Liu","year":"2013","journal-title":"Spine J."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.2147\/IJN.S60853","article-title":"Antioxidative Nanofullerol Prevents Intervertebral Disk Degeneration","volume":"9","author":"Yang","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_242","first-page":"2485","article-title":"Resveratrol Protects against Sodium Nitroprusside Induced Nucleus Pulposus Cell Apoptosis by Scavenging ROS","volume":"41","author":"Li","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"102323","DOI":"10.1016\/j.arr.2024.102323","article-title":"The Role of Oxidative Stress in Intervertebral Disc Degeneration: Mechanisms and Therapeutic Implications","volume":"98","author":"Chen","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Hernansanz-Agust\u00edn, P., and Enr\u00edquez, J.A. (2021). Generation of Reactive Oxygen Species by Mitochondria. Antioxidants, 10.","DOI":"10.3390\/antiox10030415"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/jb\/mvn057","article-title":"Evidence for Mitochondrial Localization of P5, a Member of the Protein Disulphide Isomerase Family","volume":"144","author":"Kimura","year":"2008","journal-title":"J. Biochem."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1097\/BRS.0b013e31818043b7","article-title":"Genetic and Environmental Effects on Disc Degeneration by Phenotype and Spinal Level: A Multivariate Twin Study","volume":"33","author":"Videman","year":"2008","journal-title":"Spine"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1001\/jama.285.14.1843","article-title":"Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease","volume":"285","author":"Paassilta","year":"2001","journal-title":"JAMA"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrg3142","article-title":"Epigenetics and the Environment: Emerging Patterns and Implications","volume":"13","author":"Feil","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Brown, M.K., and Naidoo, N. (2012). The Endoplasmic Reticulum Stress Response in Aging and Age-Related Diseases. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00263"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.tem.2013.06.001","article-title":"Age-Related Changes of Myocardial ATP Supply and Demand Mechanisms","volume":"24","author":"Yaniv","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"100063","DOI":"10.1016\/j.amolm.2025.100063","article-title":"Role of Antioxidants in Skin Aging and the Molecular Mechanism of ROS: A Comprehensive Review","volume":"5","author":"Hussen","year":"2025","journal-title":"Aspects Mol. Med."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1179\/174329211X13002357050897","article-title":"Age-Related Changes in an Antioxidant Defense System in Elderly Patients with Essential Hypertension Compared with Healthy Controls","volume":"16","author":"Rybka","year":"2011","journal-title":"Redox Rep."},{"key":"ref_253","doi-asserted-by":"crossref","unstructured":"Ikuno, A., Akeda, K., Takebayashi, S., Shimaoka, M., Okumura, K., and Sudo, A. (2019). Genome-Wide Analysis of DNA Methylation Profile Identifies Differentially Methylated Loci Associated with Human Intervertebral Disc Degeneration. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222188"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/8\/613\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:17:49Z","timestamp":1760030269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/8\/613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,19]]},"references-count":253,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cells14080613"],"URL":"https:\/\/doi.org\/10.3390\/cells14080613","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,19]]}}}