{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:46:09Z","timestamp":1779929169727,"version":"3.53.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Endoplasmic reticulum stress (ERS) plays a critical role in skeletal muscle physiology and pathology, though the precise mechanisms remain unclear. Salubrinal, a selective inhibitor of eIF2\u03b1 dephosphorylation, has been shown as a potential therapeutic agent for various conditions, but its effects on sarcopenia are not well understood. This study investigated the protective effects of salubrinal against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced muscle cell injury and its impact on the eIF2\u03b1\/ATF4 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gastrocnemius muscle samples from aged mice were used and cultured C2C12 myotubes were also used to explore the effects of Salubrinal through Western blotting, immunofluorescence, and apoptosis assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrated that H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment induced significant muscle cell damage, evidenced by reduced MHC1 expression and increased apoptosis. Salubrinal, in a concentration-dependent manner, mitigated these effects, preserving MHC1 expression and reducing apoptosis. Furthermore, salubrinal enhanced the expression of p-eIF2\u03b1 and ATF4, suggesting that its protective effects are mediated through the eIF2\u03b1\/ATF4 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight salubrinal\u2019s potential as a therapeutic agent for muscle wasting conditions, particularly those related to oxidative stress and ERS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1607606","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:32:15Z","timestamp":1751002335000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2\u03b1\/ATF4 signaling pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Siming","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guili","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangdi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/MCO.0000000000000362","article-title":"Role of ATF4 in skeletal muscle atrophy","volume":"20","author":"Adams","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"654940","DOI":"10.3389\/fonc.2021.654940","article-title":"Salubrinal exposes anticancer properties in inflammatory breast cancer cells by manipulating the endoplasmic reticulum stress pathway","volume":"11","author":"Alsterda","year":"2021","journal-title":"Front. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1136\/jech-2016-207321","article-title":"Socioeconomic differences in the benefits of structured physical activity compared with health education on the prevention of major mobility disability in older adults: the LIFE study","volume":"70","author":"Bann","year":"2016","journal-title":"J. Epidemiol. Community Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"982794","DOI":"10.1155\/2012\/982794","article-title":"Reactive oxygen species in skeletal muscle signaling","volume":"2012","author":"Barbieri","year":"2012","journal-title":"J. signal Transduct."},{"key":"B5","doi-asserted-by":"publisher","first-page":"7469","DOI":"10.1128\/MCB.24.17.7469-7482.2004","article-title":"Activating transcription factor 4 is translationally regulated by hypoxic stress","volume":"24","author":"Blais","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1126\/science.1065874","article-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy","volume":"294","author":"Bodine","year":"2001","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1126\/science.1101902","article-title":"A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress","volume":"307","author":"Boyce","year":"2005","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jamda.2012.10.003","article-title":"Perspective: protein supplementation during prolonged resistance type exercise training augments skeletal muscle mass and strength gains","volume":"14","author":"Cermak","year":"2013","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.bbrc.2015.11.019","article-title":"Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle","volume":"468","author":"Chalil","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11010-009-0034-4","article-title":"Role of heat shock protein 27 phosphorylation in migration of vascular smooth muscle cells","volume":"327","author":"Chen","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.3390\/biomedicines9091101","article-title":"Salubrinal enhances cancer cell death during glucose deprivation through the upregulation of xCT and mitochondrial oxidative stress","volume":"9","author":"Chen","year":"2021","journal-title":"Biomedicines"},{"key":"B12","doi-asserted-by":"publisher","first-page":"159366","DOI":"10.1016\/j.bbalip.2023.159366","article-title":"Endoplasmic reticulum stress and mitochondrial dysfunction during aging: role of sphingolipids","volume":"1868","author":"Chen","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"B13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41568-020-00312-2","article-title":"Endoplasmic reticulum stress signals in the tumour and its microenvironment","volume":"21","author":"Chen","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","article-title":"Sarcopenia","volume":"393","author":"Cruz-Jentoft","year":"2019","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fphys.2013.00236","article-title":"Endoplasmic reticulum stress in human skeletal muscle: any contribution to sarcopenia","volume":"4","author":"Deldicque","year":"2013","journal-title":"Front. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1007\/s12603-018-1139-9","article-title":"International clinical practice guidelines for sarcopenia (ICFSR): screening, diagnosis and management","volume":"22","author":"Dent","year":"2018","journal-title":"J. Nutr. Health Aging"},{"key":"B17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jconrel.2022.03.001","article-title":"Targeting autophagy, oxidative stress, and ER stress for neurodegenerative disease treatment","volume":"345","author":"Esmaeili","year":"2022","journal-title":"J. Control Release"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1016\/j.freeradbiomed.2010.08.024","article-title":"H2O2-induced mitochondrial fragmentation in C2C12 myocytes","volume":"49","author":"Fan","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.molcel.2017.05.031","article-title":"The UPR(ER): Sensor and coordinator of organismal homeostasis","volume":"66","author":"Frakes","year":"2017","journal-title":"Mol. Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1096\/fj.201800683RR","article-title":"PERK regulates skeletal muscle mass and contractile function in adult mice","volume":"33","author":"Gallot","year":"2019","journal-title":"FASEB J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e39586","DOI":"10.1371\/journal.pone.0039586","article-title":"CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress","volume":"7","author":"Ghosh","year":"2012","journal-title":"PLoS. One"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5384","DOI":"10.1007\/s12035-015-9463-0","article-title":"Endoplasmic reticulum stress instigates the rotenone induced oxidative apoptotic neuronal death: a study in rat brain","volume":"53","author":"Goswami","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/16729","article-title":"Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase","volume":"397","author":"Harding","year":"1999","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4621","DOI":"10.1172\/JCI62973","article-title":"ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth","volume":"122","author":"Hart","year":"2012","journal-title":"J. Clin. Invest."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e31204","DOI":"10.1002\/jcp.31204","article-title":"ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle","volume":"239","author":"Hinton","year":"2024","journal-title":"J. Cell. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1182\/bloodadvances.2019001139","article-title":"Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells","volume":"4","author":"Ikebe","year":"2020","journal-title":"Blood Adv."},{"key":"B27","doi-asserted-by":"publisher","first-page":"16726","DOI":"10.1074\/jbc.M300677200","article-title":"Expression of the pro-apoptotic gene gadd153\/chop is elevated in liver with aging and sensitizes cells to oxidant injury","volume":"278","author":"Ikeyama","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"453","DOI":"10.3892\/ijmm.2014.2028","article-title":"Schisandrae semen essential oil attenuates oxidative stress-induced cell damage in C2C12 murine skeletal muscle cells through Nrf2-mediated upregulation of HO-1","volume":"35","author":"Kang","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"834","DOI":"10.3389\/fonc.2020.00834","article-title":"Salubrinal in combination with 4E1RCat synergistically impairs melanoma development by disrupting the protein synthetic machinery","volume":"10","author":"Kardos","year":"2020","journal-title":"Front. Oncol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fonc.2015.00093","article-title":"Stress responses from the endoplasmic reticulum in cancer","volume":"5","author":"Kato","year":"2015","journal-title":"Front. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.1002\/jcp.27348","article-title":"Cinnamaldehyde regulates H(2) O (2) -induced skeletal muscle atrophy by ameliorating the proteolytic and antioxidant defense systems","volume":"234","author":"Kaur","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e52291","DOI":"10.7554\/eLife.52291","article-title":"Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress","volume":"9","author":"Lam","year":"2020","journal-title":"Elife"},{"key":"B33","doi-asserted-by":"publisher","first-page":"476","DOI":"10.3390\/antiox10030476","article-title":"Curcumin ameliorated oxidative stress and inflammation-related muscle disorders in C2C12 myoblast cells","volume":"10","author":"Lee","year":"2021","journal-title":"Antioxidants Basel, Switz."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3553","DOI":"10.26355\/eurrev_201806_15182","article-title":"Bioinformatics analysis of common differential genes of coronary artery disease and ischemic cardiomyopathy","volume":"22","author":"Li","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1039\/d0mt00006j","article-title":"The first copper(ii) complex with 1,10-phenanthroline and salubrinal with interesting biochemical properties","volume":"12","author":"Masuri","year":"2020","journal-title":"Metallomics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1093\/gerona\/glu129","article-title":"ER stress response in human cellular models of senescence","volume":"70","author":"Matos","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"16275","DOI":"10.3390\/ijms160716275","article-title":"Experimental evidence shows salubrinal, an eIF2\u03b1 dephosphorylation inhibitor, reduces Xenotoxicant-Induced cellular damage","volume":"16","author":"Matsuoka","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"C224","DOI":"10.1152\/ajpcell.00080.2023","article-title":"Activating transcription factor 4 regulates mitochondrial content, morphology, and function in differentiating skeletal muscle myotubes","volume":"325","author":"Memme","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/s11033-025-10415-4","article-title":"Skeletal muscle atrophy induced by aging and disuse atrophy are strongly associated with the upregulation of the endoplasmic stress protein CHOP in rats","volume":"52","author":"Michel","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1096\/fj.15-275990","article-title":"Skeletal muscle-specific eukaryotic translation initiation factor 2\u03b1 phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism","volume":"30","author":"Miyake","year":"2016","journal-title":"FASEB J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1007\/s00726-022-03176-y","article-title":"Cystine reduces mitochondrial dysfunction in C2C12 myotubes under moderate oxidative stress induced by H(2)O(2)","volume":"54","author":"Mizugaki","year":"2022","journal-title":"Amino Acids"},{"key":"B42","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12964-022-00865-9","article-title":"Endoplasmic reticulum stress downregulates PGC-1\u03b1 in skeletal muscle through ATF4 and an mTOR-mediated reduction of CRTC2","volume":"20","author":"Montori-Grau","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e0122654","DOI":"10.1371\/journal.pone.0122654","article-title":"Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells","volume":"10","author":"Mougeolle","year":"2015","journal-title":"PLoS One"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3692","DOI":"10.1002\/jcb.24242","article-title":"CHOP down-regulates cFLIP(L) expression by promoting ubiquitin\/proteasome-mediated cFLIP(L) degradation","volume":"113","author":"Noh","year":"2012","journal-title":"J. Cell Biochem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1001\/jama.2014.5616","article-title":"Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial","volume":"311","author":"Pahor","year":"2014","journal-title":"JAMA"},{"key":"B46","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.bbrc.2014.05.143","article-title":"Activation of ER stress by hydrogen peroxide in C2C12 myotubes","volume":"450","author":"Pierre","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1083\/jcb.201702058","article-title":"Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals","volume":"216","author":"Quir\u00f3s","year":"2017","journal-title":"J. Cell Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3390\/ijms21010169","article-title":"Endoplasmic reticulum stress pathway, the unfolded protein response, modulates immune function in the tumor microenvironment to impact tumor progression and therapeutic response","volume":"21","author":"Ramirez","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3838","DOI":"10.4161\/cc.8.23.10086","article-title":"Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia","volume":"8","author":"Rzymski","year":"2009","journal-title":"Cell Cycle"},{"key":"B50","doi-asserted-by":"publisher","first-page":"4294","DOI":"10.1111\/febs.12253","article-title":"Mechanisms regulating skeletal muscle growth and atrophy","volume":"280","author":"Schiaffino","year":"2013","journal-title":"FEBS J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00223-017-0277-0","article-title":"Epidemiology of sarcopenia: determinants throughout the lifecourse","volume":"101","author":"Shaw","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"B52","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.lfs.2009.01.014","article-title":"Apoptotic signaling induced by H2O2-mediated oxidative stress in differentiated C2C12 myotubes","volume":"84","author":"Siu","year":"2009","journal-title":"LIFE Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.jamda.2012.05.020","article-title":"Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial","volume":"13","author":"Tieland","year":"2012","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"B54","doi-asserted-by":"publisher","first-page":"112534","DOI":"10.1016\/j.celrep.2023.112534","article-title":"Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2","volume":"42","author":"Vidak","year":"2023","journal-title":"Cell Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.cellsig.2016.05.007","article-title":"Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic \u03b2 cells","volume":"28","author":"Wang","year":"2016","journal-title":"Cell. Signal."},{"key":"B56","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.tiv.2017.10.006","article-title":"Eukaryotic translation initiation factor 2 subunit \u03b1 (eIF2\u03b1) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2\u03b1 signaling pathway","volume":"46","author":"Wang","year":"2018","journal-title":"Toxicol Vitro"},{"key":"B57","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1161\/CIRCRESAHA.122.321050","article-title":"ATF4 protects the heart from failure by antagonizing oxidative stress","volume":"131","author":"Wang","year":"2022","journal-title":"Circ. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"3501","DOI":"10.3390\/ijms22073501","article-title":"Salubrinal alleviates collagen-induced arthritis through promoting P65 degradation in osteoclastogenesis","volume":"22","author":"Wang","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/s41420-023-01365-6","article-title":"TNF-\u03b1 contributes to sarcopenia through caspase-8\/caspase-3\/GSDME-mediated pyroptosis","volume":"9","author":"Wu","year":"2023","journal-title":"Cell Death Discov."},{"key":"B60","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1021\/acsbiomaterials.0c01802","article-title":"eIF2\u03b1-ATF4 pathway activated by a change in the calcium environment participates in BCP-mediated bone regeneration","volume":"7","author":"Xiang","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"B61","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s12013-015-0659-8","article-title":"Astragalus polysaccharide inhibits autophagy and apoptosis from peroxide-induced injury in C2C12 myoblasts","volume":"73","author":"Yin","year":"2015","journal-title":"Cell biochem. Biophys."},{"key":"B62","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s11010-011-1076-y","article-title":"Human tissue kallikrein 1 gene delivery inhibits PDGF-BB-induced vascular smooth muscle cells proliferation and upregulates the expressions of p27Kip1 and p2lCip1","volume":"360","author":"Yu","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/7468738","article-title":"Neuroprotective effect of the inhibitor salubrinal after cardiac arrest in a rodent model","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B64","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1002\/jcp.30950","article-title":"Endoplasmic reticulum stress promotes sepsis-induced muscle atrophy via activation of STAT3 and Smad3","volume":"238","author":"Zheng","year":"2023","journal-title":"J. Cell Physiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s11010-018-3480-z","article-title":"CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension","volume":"455","author":"Zhuang","year":"2019","journal-title":"Mol. Cell. Biochem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1607606\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:32:16Z","timestamp":1751002336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1607606\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":65,"alternative-id":["10.3389\/fphar.2025.1607606"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1607606","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]},"article-number":"1607606"}}