{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:35:31Z","timestamp":1785936931515,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Schweizerischer Nationalfonds zur F&amp;#x00F6;rderung der Wissenschaftlichen Forschung","award":["179434"],"award-info":[{"award-number":["179434"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>It is estimated that over 1.5 billion people suffer from various forms of chronic liver disease worldwide. The emerging prevalence of metabolic syndromes and alcohol misuse, along with the lack of disease-modifying agents for the therapy of many severe liver conditions predicts that chronic liver disease will continue to be a major problem in the future. Better understanding of the underlying pathogenetic mechanisms and identification of potential therapeutic targets remains a priority. Herein, we explored the potential role of the 3-mercaptopyruvate sulfurtransferase\/hydrogen sulfide (H2S) system in the regulation of the endoplasmic reticulum (ER) stress and of its downstream processes in the immortalized hepatic cell line HepG2 in vitro. ER stress suppressed endogenous H2S levels and pharmacological supplementation of H2S with sodium hydrogen sulfide (NaHS) mitigated many aspects of ER stress, culminating in improved cellular bioenergetics and prevention of autophagic arrest, thereby switching cells\u2019 fate towards survival. Genetic silencing of 3-MST or pharmacological inhibition of the key enzymes involved in hepatocyte H2S biosynthesis exacerbated many readouts related to ER-stress or its downstream functional responses. Our findings implicate the 3-MST\/H2S system in the intracellular network that governs proteostasis and ER-stress adaptability in hepatocytes and reinforce the therapeutic potential of pharmacological H2S supplementation.<\/jats:p>","DOI":"10.3390\/biom10121692","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"1692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of Hydrogen Sulfide and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of the Endoplasmic Reticulum Stress Response in Hepatocytes"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-7107","authenticated-orcid":false,"given":"Theodora","family":"Panagaki","sequence":"first","affiliation":[{"name":"Chair of Pharmacology, Section of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa B.","family":"Randi","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-4235","authenticated-orcid":false,"given":"Csaba","family":"Szabo","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-18144-8_1","article-title":"H2S synthesizing enzymes: Biochemistry and molecular aspects","volume":"230","author":"Huang","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-3-319-18144-8_3","article-title":"Physiological roles of hydrogen sulfide and polysulfides","volume":"230","author":"Kimura","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1124\/pr.117.014050","article-title":"International union of basic and clinical pharmacology. CII: Pharmacological modulation of H2S levels: H2S donors and H2S biosynthesis inhibitors","volume":"69","author":"Szabo","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.bcp.2017.09.010","article-title":"A timeline of hydrogen sulfide (H2S) research: From environmental toxin to biological mediator","volume":"149","author":"Szabo","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/bph.14100","article-title":"Multiple role of 3-mercaptopyruvate sulfurtransferase: Antioxidative function, H2S and polysulfide production and possible SOx production","volume":"175","author":"Nagahara","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104083","DOI":"10.1016\/j.phrs.2018.11.034","article-title":"Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway in cancer cells","volume":"154","author":"Augsburger","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1055\/s-0039-1681032","article-title":"Endoplasmic reticulum stress in metabolic liver diseases and hepatic fibrosis","volume":"39","author":"Maiers","year":"2019","journal-title":"Semin. Liver Dis."},{"key":"ref_9","first-page":"192","article-title":"Calcium signaling in liver injury and regeneration","volume":"5","author":"Hankeova","year":"2018","journal-title":"Front. Med. (Lausanne)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40227","DOI":"10.1038\/srep40227","article-title":"Discovery and mechanistic characterization of selective inhibitors of H2S-producing enzyme: 3-mercaptopyruvate sulfurtransferase (3MST) targeting active-site cysteine persulfide","volume":"7","author":"Hanaoka","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Panagaki, T., Randi, E.B., and Szabo, C. (2020). Role of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation and cellular bioenergetics in human Down syndrome fibroblasts. Biomolecules, 10.","DOI":"10.3390\/biom10040653"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.niox.2014.04.008","article-title":"AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in vitro","volume":"41","author":"Szczesny","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/s41598-017-16488-x","article-title":"Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells","volume":"7","author":"Panagaki","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ceca.2018.09.005","article-title":"Nonlinear relationship between ER Ca2+ depletion versus induction of the unfolded protein response, autophagy inhibition, and cell death","volume":"76","author":"Szalai","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1089\/ars.2010.3482","article-title":"Autophagosome formation and molecular mechanism of autophagy","volume":"14","author":"Tanida","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","first-page":"e00272-18","article-title":"H2S, a bacterial defense mechanism against the host immune response","volume":"87","author":"Cui","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Augsburger, F., Randi, E.B., Jendly, M., Ascencao, K., Dilek, N., and Szabo, C. (2020). Role of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation, migration, and bioenergetics in murine colon cancer cells. Biomolecules, 10.","DOI":"10.3390\/biom10030447"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/bph.14574","article-title":"3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics","volume":"177","author":"Szaniszlo","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1111\/bph.12171","article-title":"Selectivity of commonly used pharmacological inhibitors for cystathionine \u03b2 synthase (CBS) and cystathionine \u03b3 lyase (CSE)","volume":"169","author":"Asimakopoulou","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zuhra, K., Augsburger, F., Majtan, T., and Szabo, C. (2020). Cystathionine-\u03b2-synthase: Molecular regulation and pharmacological inhibition. Biomolecules, 10.","DOI":"10.3390\/biom10050697"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12474","DOI":"10.1073\/pnas.1306241110","article-title":"Tumor-derived hydrogen sulfide, produced by cystathionine-\u03b2-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer","volume":"110","author":"Szabo","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2119\/molmed.2016.00102","article-title":"Cystathionine-beta-synthase inhibition for colon cancer: Enhancement of the efficacy of aminooxyacetic acid via the prodrug approach","volume":"22","author":"Chao","year":"2016","journal-title":"Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2016.05.001","article-title":"Malate-aspartate shuttle inhibitor aminooxyacetic acid leads to decreased intracellular ATP levels and altered cell cycle of C6 glioma cells by inhibiting glycolysis","volume":"378","author":"Wang","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36125","DOI":"10.1038\/srep36125","article-title":"Inhibition of hydrogen sulfide biosynthesis sensitizes lung adenocarcinoma to chemotherapeutic drugs by inhibiting mitochondrial DNA repair and suppressing cellular bioenergetics","volume":"6","author":"Szczesny","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bcp.2017.10.007","article-title":"Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells","volume":"149","author":"Untereiner","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18769","DOI":"10.1073\/pnas.1911895116","article-title":"Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome","volume":"116","author":"Panagaki","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1615\/JEnvironPatholToxicolOncol.2020034851","article-title":"Cystathionine \u03b2 synthase\/hydrogen sulfide signaling in multiple myeloma regulates cell proliferation and apoptosis","volume":"39","author":"Zhang","year":"2020","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118348","DOI":"10.1016\/j.lfs.2020.118348","article-title":"Inhibition of endogenous hydrogen sulfide biosynthesis enhances the anti-cancer effect of 3,3\u2032-diindolylmethane in human gastric cancer cells","volume":"261","author":"Ye","year":"2020","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.7150\/jca.35375","article-title":"Aminooxyacetic acid (AOAA) sensitizes colon cancer cells to oxaliplatin via exaggerating apoptosis induced by ROS","volume":"11","author":"Yue","year":"2020","journal-title":"J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1073\/pnas.87.7.2466","article-title":"Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase","volume":"87","author":"Thastrup","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1146\/annurev.biochem.73.011303.074134","article-title":"The mammalian unfolded protein response","volume":"74","author":"Kaufman","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105218","DOI":"10.1016\/j.phrs.2020.105218","article-title":"Endoplasmic reticulum stress and protein degradation in chronic liver disease","volume":"161","author":"Xia","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature11058","article-title":"Sustained translational repression by eIF2\u03b1-P mediates prion neurodegeneration","volume":"485","author":"Moreno","year":"2012","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ncb0311-184","article-title":"Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress","volume":"13","author":"Tabas","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jcp.24459","article-title":"Calnexin silencing in mouse neonatal cardiomyocytes induces Ca2+ cycling defects, ER stress, and apoptosis","volume":"229","author":"Bousette","year":"2014","journal-title":"J. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1101\/gad.1250704","article-title":"CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum","volume":"18","author":"Marciniak","year":"2004","journal-title":"Genes Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1083\/jcb.200904060","article-title":"Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis","volume":"186","author":"Li","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1016\/j.bbamcr.2014.03.022","article-title":"Calcium trafficking integrates endoplasmic reticulum function with mitochondrial bioenergetics","volume":"1843","author":"Kaufman","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/hmg\/dds472","article-title":"Protein disulfide isomerase in ALS mouse glia links protein misfolding with NADPH oxidase-catalyzed superoxide production","volume":"22","author":"Jaronen","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","first-page":"3831713","article-title":"Hydrogen sulfide as a novel regulatory factor in liver health and disease","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sun, H.-J., Wu, Z.-Y., Nie, X.-W., Wang, X.-Y., and Bian, J.-S. (2020). Implications of hydrogen sulfide in liver pathophysiology: Mechanistic insights and therapeutic potential. J. Adv. Res., in press.","DOI":"10.1016\/j.jare.2020.05.010"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1002\/lt.21810","article-title":"Role of hydrogen sulfide in hepatic ischemia-reperfusion\u2013induced injury in rats","volume":"15","author":"Kang","year":"2009","journal-title":"Liver Transpl."},{"key":"ref_44","first-page":"924","article-title":"Protection of CSE\/H2S system in hepatic ischemia reperfusion injury in rats","volume":"48","author":"Kang","year":"2010","journal-title":"Zhonghua Wai Ke Za Zhi"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.lfs.2010.10.004","article-title":"Curative effects of hydrogen sulfide against acetaminophen-induced hepatotoxicity in mice","volume":"87","author":"Morsy","year":"2010","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tan, G., Pan, S., Li, J., Dong, X., Kang, K., Zhao, M., Jiang, X., Kanwar, J.R., Qiao, H., and Jiang, H. (2011). Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025943"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13618-014-0022-y","article-title":"Exogenous hydrogen sulfide mitigates the fatty liver in obese mice through improving lipid metabolism and antioxidant potential","volume":"5","author":"Wu","year":"2015","journal-title":"Med. Gas Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.4161\/auto.25900","article-title":"Modulation of intracellular calcium homeostasis blocks autophagosome formation","volume":"9","author":"Engedal","year":"2013","journal-title":"Autophagy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.molcel.2011.04.024","article-title":"Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest","volume":"42","author":"Ganley","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jhep.2019.01.026","article-title":"Autophagy in liver diseases: Time for translation?","volume":"70","author":"Allaire","year":"2019","journal-title":"J. Hep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.phrs.2018.03.002","article-title":"Hydrogen sulfide and autophagy: A double edged sword","volume":"131","author":"Wu","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1002\/jcp.25785","article-title":"Crosstalk of autophagy and apoptosis: Involvement of the dual role of autophagy under ER stress","volume":"232","author":"Song","year":"2017","journal-title":"J. Cell Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7683","DOI":"10.1093\/nar\/gkt563","article-title":"The eIF2\u03b1\/ATF4 pathway is essential for stress-induced autophagy gene expression","volume":"41","author":"Maurin","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_54","first-page":"1","article-title":"Dual role for CHOP in the crosstalk between autophagy and apoptosis to determine cell fate in response to amino acid deprivation","volume":"26","author":"Chaveroux","year":"2014","journal-title":"Cell Signal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16567","DOI":"10.1074\/jbc.M700605200","article-title":"H2S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells","volume":"282","author":"Yang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/SHK.0000000000000759","article-title":"Modeling acute ER stress in vivo and in vitro","volume":"47","author":"Abdullahi","year":"2017","journal-title":"Shock"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1089\/ars.2009.2898","article-title":"Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic endoplasmic reticulum stress in rats","volume":"12","author":"Wei","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.niox.2014.12.013","article-title":"Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress","volume":"46","author":"Barr","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3892\/mmr.2016.5289","article-title":"Hydrogen sulfide exhibits cardioprotective effects by decreasing endoplasmic reticulum stress in a diabetic cardiomyopathy rat model","volume":"14","author":"Li","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"E190","DOI":"10.1152\/ajpendo.00196.2016","article-title":"Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes","volume":"312","author":"Yang","year":"2017","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"64203","DOI":"10.18632\/oncotarget.19448","article-title":"Hydrogen sulfide ameliorates cognitive dysfunction in streptozotocin-induced diabetic rats: Involving suppression in hippocampal endoplasmic reticulum stress","volume":"8","author":"Zou","year":"2017","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"C609","DOI":"10.1152\/ajpcell.00147.2018","article-title":"Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury","volume":"315","author":"Majumder","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"BSR20190304","DOI":"10.1042\/BSR20190304","article-title":"H2S attenuates endoplasmic reticulum stress in hypoxia-induced pulmonary artery hypertension","volume":"39","author":"Wu","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/fcp.12543","article-title":"Endogenous hydrogen sulfide alleviates methotrexate-induced cognitive impairment by attenuating endoplasmic reticulum stress-induced apoptosis via CHOP and caspase-12","volume":"34","author":"Lv","year":"2020","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.lfs.2015.11.025","article-title":"Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway","volume":"144","author":"Ying","year":"2016","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cell.2018.03.001","article-title":"Amino acid restriction triggers angiogenesis via GCN2\/ATF4 regulation of VEGF and H2S Production","volume":"173","author":"Longchamp","year":"2018","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1091\/mbc.e09-02-0133","article-title":"Induction of liver steatosis and lipid droplet formation in ATF6alpha-knockout mice burdened with pharmacological endoplasmic reticulum stress","volume":"21","author":"Yamamoto","year":"2010","journal-title":"Mol. Biol. Cell."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.1074\/jbc.M115.697102","article-title":"Mitochondrial sulfide quinone oxidoreductase prevents activation of the unfolded protein response in hydrogen sulfide","volume":"291","author":"Horsman","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mad.2016.11.005","article-title":"New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of endogenous H2S production and ER stress","volume":"162","author":"Guo","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_70","first-page":"754","article-title":"Hydrogen sulfide intervention in cystathionine-\u03b2-synthase mutant mouse helps restore ocular homeostasis","volume":"12","author":"George","year":"2019","journal-title":"Int. J. Ophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.devcel.2008.10.015","article-title":"UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators","volume":"15","author":"Rutkowski","year":"2008","journal-title":"Dev. Cell."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2337\/db15-1637","article-title":"Hepatic ATF6 increases fatty acid oxidation to attenuate hepatic steatosis in mice through peroxisome proliferator-activated receptor \u03b1","volume":"65","author":"Chen","year":"2016","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13143","DOI":"10.1074\/jbc.M117.778654","article-title":"Hydrogen sulfide modulates eukaryotic translation initiation factor 2\u03b1 (eIF2\u03b1) phosphorylation status in the integrated stress-response pathway","volume":"292","author":"Yadav","year":"2017","journal-title":"J. Biol. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/12\/1692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:50Z","timestamp":1760179610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/12\/1692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":73,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["biom10121692"],"URL":"https:\/\/doi.org\/10.3390\/biom10121692","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}