{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:14Z","timestamp":1787027834259,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HI 813\/8-1"],"award-info":[{"award-number":["HI 813\/8-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The administration of adipose tissue-derived mesenchymal stem cells (ADMSCs) represents a promising therapeutic option after myocardial ischemia or myocardial infarction. However, their potential is reduced due to the high post-transplant cell mortality probably caused by oxidative stress and mitogen-deficient microenvironments. To identify protection strategies for ADMSCs, this study investigated the influence of the non-psychoactive phytocannabinoid cannabidiol (CBD) and the endocannabinoid analogue R(+)-methanandamide (MA) on the induction of heme oxygenase-1 (HO-1) and autophagy under serum-free conditions. At a concentration of 3 \u00b5M, CBD induced an upregulation of HO-1 mRNA and protein within 6 h, whereas for MA only a late and comparatively lower increase in the HO-1 protein could be detected after 48 h. In addition, both cannabinoids induced time- and concentration-dependent increases in LC3A\/B-II protein, a marker of autophagy, and in metabolic activity. A participation of several cannabinoid-binding receptors in the effect on metabolic activity and HO-1 was excluded. Similarly, knockdown of HO-1 by siRNA or inhibition of HO-1 activity by tin protoporphyrin IX (SnPPIX) had no effect on CBD-induced autophagy and metabolic activity. On the other hand, the inhibition of autophagy by bafilomycin A1 led to a significant decrease in cannabinoid-induced metabolic activity and to an increase in apoptosis. Under these circumstances, a significant induction of HO-1 expression after 24 h could also be demonstrated for MA. Remarkably, inhibition of HO-1 by SnPPIX under conditions of autophagy deficit led to a significant reversal of apoptosis in cannabinoid-treated cells. In conclusion, the investigated cannabinoids increase metabolic viability of ADMSCs under serum-free conditions by inducing HO-1-independent autophagy but contribute to apoptosis under conditions of additional autophagy deficit via an HO-1-dependent pathway.<\/jats:p>","DOI":"10.3390\/cells9102298","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T21:42:21Z","timestamp":1602798141000},"page":"2298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions"],"prefix":"10.3390","volume":"9","author":[{"given":"Katharina","family":"Bublitz","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"B\u00f6ckmann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-176X","authenticated-orcid":false,"given":"Kirsten","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Hinz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage cells from human adipose tissue: Implications for cell-based therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/01.CIR.0000121425.42966.F1","article-title":"Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells","volume":"109","author":"Rehman","year":"2004","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1089\/scd.2012.0201","article-title":"Paracrine release from nonviral engineered adipose-derived stem cells promotes endothelial cell survival and migration in vitro","volume":"22","author":"Deveza","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/CRD.0b013e3181620e3b","article-title":"Therapeutic angiogenesis: A new treatment approach for ischemic heart disease\u2013part I","volume":"16","author":"Ahn","year":"2008","journal-title":"Cardiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"I31","DOI":"10.1161\/CIRCULATIONAHA.106.680157","article-title":"Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes","volume":"116","author":"Boodhwani","year":"2007","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/term.452","article-title":"Adipose tissue and bone marrow-derived stem cells react similarly in an ischaemia-like microenvironment","volume":"6","author":"Tse","year":"2012","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1017\/S0029665113003649","article-title":"Elevating endocannabinoid levels: Pharmacological strategies and potential therapeutic applications","volume":"73","author":"Pertwee","year":"2014","journal-title":"Proc. Nutr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/bph.14426","article-title":"Anti-tumour actions of cannabinoids","volume":"176","author":"Hinz","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"H3602","DOI":"10.1152\/ajpheart.00098.2007","article-title":"Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury","volume":"293","author":"Durst","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1755-5922.2010.00233.x","article-title":"The potential for clinical use of cannabinoids in treatment of cardiovascular diseases","volume":"29","author":"Durst","year":"2011","journal-title":"Cardiovasc. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.plipres.2013.05.004","article-title":"Cannabinoid receptor signaling in progenitor\/stem cell proliferation and differentiation","volume":"52","author":"Bari","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bcp.2013.11.016","article-title":"Increase of mesenchymal stem cell migration by cannabidiol via activation of p42\/44 MAPK","volume":"87","author":"Schmuhl","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1194\/jlr.M061473","article-title":"Inhibition of FAAH confers increased stem cell migration via PPAR\u03b1","volume":"56","author":"Wollank","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105984","DOI":"10.18632\/oncotarget.22517","article-title":"Decisive role of P42\/44 mitogen-activated protein kinase in \u0394(9)-tetrahydrocannabinol-induced migration of human mesenchymal stem cells","volume":"8","author":"Ramer","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","first-page":"111","article-title":"Adaptive responses to tissue injury: Role of heme oxygenase-1","volume":"124","author":"Agarwal","year":"2013","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1620\/tjem.226.231","article-title":"Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits","volume":"226","author":"Yang","year":"2012","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.transproceed.2013.12.013","article-title":"Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats","volume":"46","author":"Chen","year":"2014","journal-title":"Transplant. Proc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17974","DOI":"10.3390\/ijms151017974","article-title":"Curcumin-induced heme oxygenase-1 expression prevents H2O2-induced cell death in wild type and heme oxygenase-2 knockout adipose-derived mesenchymal stem cells","volume":"15","author":"Cremers","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.cellbi.2008.07.010","article-title":"Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement","volume":"32","author":"Zeng","year":"2008","journal-title":"Cell. Biol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1002\/hep.24324","article-title":"Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection\/sepsis in mice","volume":"53","author":"Carchman","year":"2011","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zhang, L., Qiao, Y., Zhou, X., Wu, G., Wang, L., Peng, Y., Dong, X., Huang, H., and Si, L. (2013). Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075927"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.3390\/ijms15011625","article-title":"Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy","volume":"15","author":"Lin","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1152\/physrev.00030.2009","article-title":"Regulation of mammalian autophagy in physiology and pathophysiology","volume":"90","author":"Ravikumar","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/cr.2011.200","article-title":"Autophagy is required for self-renewal and differentiation of adult human stem cells","volume":"22","author":"Salemi","year":"2012","journal-title":"Cell. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature11895","article-title":"FOXO3A directs a protective autophagy program in haematopoietic stem cells","volume":"494","author":"Warr","year":"2013","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.15252\/embj.201488278","article-title":"Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation","volume":"33","author":"Tang","year":"2014","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/biores.2014.0032","article-title":"Enhanced Autophagy of Adipose-Derived Stem Cells Grown on Chitosan Substrates","volume":"4","author":"Yang","year":"2015","journal-title":"Biores. Open Access"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.yexcr.2016.09.013","article-title":"Downregulation of Nrf2 promotes autophagy-dependent osteoblastic differentiation of adipose-derived mesenchymal stem cells","volume":"349","author":"Tao","year":"2016","journal-title":"Exp. Cell. Res."},{"key":"ref_30","first-page":"951","article-title":"Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors","volume":"299","author":"Jacobsson","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2004.09.058","article-title":"Species comparison and pharmacological characterization of rat and human CB2 cannabinoid receptors","volume":"505","author":"Mukherjee","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/jnci\/djm268","article-title":"Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1","volume":"100","author":"Ramer","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fcell.2016.00080","article-title":"Therapeutic Efficacy of Stem Cells Transplantation in Diabetes: Role of Heme Oxygenase","volume":"4","author":"Raffaele","year":"2016","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/emmm.201201999","article-title":"Autophagic control of cell \u2018stemness\u2019","volume":"5","author":"Pan","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1089\/scd.2012.0124","article-title":"Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells","volume":"21","author":"Oliver","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34595","DOI":"10.18632\/oncotarget.26191","article-title":"Up-regulation of heme oxygenase-1 expression and inhibition of disease-associated features by cannabidiol in vascular smooth muscle cells","volume":"9","author":"Schwartz","year":"2018","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"B\u00f6ckmann, S., and Hinz, B. (2020). Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy. Cells, 9.","DOI":"10.3390\/cells9071703"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/molehr\/gas049","article-title":"Uncovering a role for endocannabinoid signaling in autophagy in preimplantation mouse embryos","volume":"19","author":"Oh","year":"2013","journal-title":"Mol. Human Repr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20150568","article-title":"KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity","volume":"469","author":"Dodson","year":"2015","journal-title":"Biochem. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4161\/auto.7.3.14044","article-title":"Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway","volume":"7","author":"Waltz","year":"2011","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.lfs.2015.10.014","article-title":"Propofol-enhanced autophagy increases motility and angiogenic capacity of cultured human umbilical vascular endothelial cells","volume":"142","author":"Chang","year":"2015","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"L280","DOI":"10.1152\/ajplung.00097.2015","article-title":"Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice","volume":"309","author":"Surolia","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.cbi.2016.07.020","article-title":"6-Gingerol induces autophagy to protect HUVECs survival from apoptosis","volume":"256","author":"Wang","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbalip.2013.09.004","article-title":"tert-Butylhydroquinone (tBHQ) protects hepatocytes against lipotoxicity via inducing autophagy independently of Nrf2 activation","volume":"1841","author":"Li","year":"2014","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bbrc.2016.09.037","article-title":"Heme oxygenase-1-mediated apoptosis under cadmium-induced oxidative stress is regulated by autophagy, which is sensitized by tumor suppressor p53","volume":"479","author":"So","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1089\/scd.2011.0684","article-title":"Autophagy activation: A novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase\/mammalian target of rapamycin pathway","volume":"21","author":"Zhang","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.15252\/embj.201490272","article-title":"How stem cells get \u201cturned on\u201d","volume":"33","author":"Wagers","year":"2014","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13287-018-1029-4","article-title":"Inhibition of autophagy promoted high glucose\/ROS-mediated apoptosis in ADSCs","volume":"9","author":"Li","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1073\/pnas.84.8.2464","article-title":"Dual control mechanism for heme oxygenase: Tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver","volume":"84","author":"Sardana","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H999","DOI":"10.1152\/ajpheart.01289.2007","article-title":"Inhibition of vascular smooth muscle cell proliferation by chronic hemin treatment","volume":"295","author":"Chang","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1038\/onc.2014.166","article-title":"Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity","volume":"34","author":"Hsu","year":"2015","journal-title":"Oncogene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"28868","DOI":"10.18632\/oncotarget.7563","article-title":"Heme oxygenase-1 nuclear translocation regulates bortezomib-induced cytotoxicity and mediates genomic instability in myeloma cells","volume":"7","author":"Tibullo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"26882","DOI":"10.1074\/jbc.M114.567685","article-title":"Nuclear heme oxygenase-1 (HO-1) modulates subcellular distribution and activation of Nrf2, impacting metabolic and anti-oxidant defenses","volume":"289","author":"Biswas","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1128\/MCB.00248-10","article-title":"A noncanonical mechanism of Nrf2 activation by autophagy deficiency: Direct interaction between Keap1 and p62","volume":"30","author":"Lau","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1083\/jcb.201102031","article-title":"Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells","volume":"193","author":"Inami","year":"2011","journal-title":"J. Cell. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/ncb2021","article-title":"The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1","volume":"12","author":"Komatsu","year":"2010","journal-title":"Nat. Cell. Biol."},{"key":"ref_57","first-page":"2162","article-title":"Autophagy inhibition promotes epithelial-mesenchymal transition through ROS\/HO-1 pathway in ovarian cancer cells","volume":"6","author":"Zhao","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/jpet.115.226431","article-title":"Autophagy Deficiency Diminishes Indomethacin-Induced Intestinal Epithelial Cell Damage through Activation of the ERK\/Nrf2\/HO-1 Pathway","volume":"355","author":"Harada","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"794237","DOI":"10.1155\/2012\/794237","article-title":"Regulation of ROS production and vascular function by carbon monoxide","volume":"2012","author":"Choi","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.redox.2013.07.004","article-title":"Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity","volume":"2","author":"Bansal","year":"2013","journal-title":"Redox Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1089\/ars.2010.3587","article-title":"Sustained activation of nuclear erythroid 2-related factor 2\/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice","volume":"14","author":"Rajasekaran","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.3390\/ijms19082260","article-title":"Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?","volume":"19","author":"Nitti","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.mehy.2014.09.022","article-title":"Enhancing stem cell survival in an ischemic heart by CRISPR-dCas9-based gene regulation","volume":"83","author":"Pan","year":"2014","journal-title":"Med. Hypotheses"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1387-2656(05)11004-7","article-title":"Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction","volume":"11","author":"Berridge","year":"2005","journal-title":"Biotechnol. Annu. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.4161\/auto.25418","article-title":"Autophagy protects kidney proximal tubule epithelial cells from mitochondrial metabolic stress","volume":"9","author":"Kimura","year":"2013","journal-title":"Autophagy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1101\/gad.283416.116","article-title":"Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells","volume":"30","author":"Guo","year":"2016","journal-title":"Genes Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.redox.2016.12.029","article-title":"Cannabidiol attenuates OGD\/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons","volume":"11","author":"Sun","year":"2017","journal-title":"Redox Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2119\/molmed.2014.00261","article-title":"Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis","volume":"21","author":"Hao","year":"2015","journal-title":"Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/cas.12712","article-title":"Src\/STAT3-dependent heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to doxorubicin by promoting autophagy","volume":"106","author":"Tan","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.1111\/jcmm.13800","article-title":"Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K\/Akt pathway","volume":"22","author":"Pei","year":"2018","journal-title":"J. Cell. Mol. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:21:40Z","timestamp":1760178100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,15]]},"references-count":70,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cells9102298"],"URL":"https:\/\/doi.org\/10.3390\/cells9102298","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,15]]}}}