{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:18:57Z","timestamp":1782861537953,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"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. Cell Dev. Biol."],"abstract":"<jats:p>SO<jats:sub>2<\/jats:sub>, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO<jats:sub>2<\/jats:sub> acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO<jats:sub>2<\/jats:sub> on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO<jats:sub>2<\/jats:sub> can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO<jats:sub>2<\/jats:sub> is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.<\/jats:p>","DOI":"10.3389\/fcell.2021.729728","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T11:26:31Z","timestamp":1633692391000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Endogenous SO2 Controls Cell Apoptosis: The State-of-the-Art"],"prefix":"10.3389","volume":"9","author":[{"given":"Yingying","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiantong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.bbrc.2003.10.055","article-title":"Identification of carbonyl sulfide and sulfur dioxide in porcine coronary artery by gas chromatography\/mass spectrometry, possible relevance to EDHF.","volume":"331","author":"Balazy","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s00380-011-0192-7","article-title":"Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury.","volume":"27","author":"Chen","year":"2012","journal-title":"Heart Vessels"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1852-x","article-title":"Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure.","author":"Chen","year":"2021","journal-title":"Sci. China Life Sci."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020436","article-title":"Macrophages in lung injury, repair, and fibrosis.","volume":"10","author":"Cheng","year":"2021","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1021\/acschembio.6b00106","article-title":"Benzothiazole sulfinate: a water-soluble and slow-releasing sulfur dioxide donor.","volume":"11","author":"Day","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/jbbrc.2018.01.103","article-title":"Retina-derived endogenous sulfur dioxide might be a novel anti-apoptotic factor.","volume":"496","author":"Du","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1111\/j.1745-7254.2008.00845.x","article-title":"Endogenously generated sulfur dioxide and its vasorelaxant effect in rats.","volume":"29","author":"Du","year":"","journal-title":"Acta Pharmacol. Sin"},{"key":"B8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3969\/j.issn.1003-515X.2008.01.007","article-title":"Influence of sulfur dioxide and its derivatives on rats\u2019 blood pressure.","volume":"23","author":"Du","year":"","journal-title":"J. Appl. Clin. Pediatr."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105599","article-title":"Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis.","volume":"168","author":"Duan","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B10","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/S0021-9258(18)33025-4","article-title":"Cysteinesulfinate metabolism: altered partitioning between transamination and decarboxylation following administration of beta-methyleneaspartate.","volume":"258","author":"Griffith","year":"1983","journal-title":"J. Biol. Chem"},{"key":"B11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.neulet.2013.12.042","article-title":"Dose-dependent effect of sulfur dioxide on brain damage induced by recurrent febrile seizures in rats.","volume":"563","author":"Han","year":"2014","journal-title":"Neurosci. lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3321\/j.issn:0371-0874.2009.05.014","article-title":"Ameliorative effects of exogenous sulfur dioxide on lipopolysaccharide-induced acute lung injury in rats.","volume":"61","author":"Huang","year":"2009","journal-title":"Acta Physiol. Sin."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8961951","article-title":"Endogenous sulfur dioxide: a new member of gasotransmitter family in the cardiovascular system.","volume":"2016","author":"Huang","year":"2016","journal-title":"Oxid. Med. Cell. Longev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.scib.2021.04.00","article-title":"Endogenous sulfur dioxide is a new gasotransmitter with promising therapeutic potential in cardiovascular system.","volume":"66","author":"Huang","year":"2021","journal-title":"Sci. Bull"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.2147\/IJGM.S312058","article-title":"Plasma endogenous sulfur dioxide: a novel biomarker to predict acute kidney injury in critically Ill patients.","volume":"14","author":"Jiang","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"10465","DOI":"10.3390\/ijms140510465","article-title":"The role of sulfur dioxide in the regulation of mitochondrion-related cardiomyocyte apoptosis in rats with isopropylarterenol-induced myocardial injury.","volume":"14","author":"Jin","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s00726-010-0510-x","article-title":"Hydrogen sulfide: its production, release and functions.","volume":"41","author":"Kimura","year":"2011","journal-title":"Amino Acids"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00075198-200102000-00001","article-title":"Neutrophil activation and acute lung injury.","volume":"7","author":"Lee","year":"2001","journal-title":"Curr. Opin. Crit Care."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8758","DOI":"10.1007\/s11356-019-04319-7","article-title":"Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes.","volume":"26","author":"Li","year":"2019","journal-title":"Environ. Sci. Pollut. Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/labinvest.2010.156","article-title":"Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats.","volume":"91","author":"Liang","year":"2011","journal-title":"Lab. Invest."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.229","article-title":"Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the ERK\/MAP kinase pathway mediated by cAMP\/PKA signaling.","volume":"5","author":"Liu","year":"2014","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"8953","DOI":"10.3892\/mmr.2017.7714","article-title":"Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats.","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"999","DOI":"10.3760\/cma.j.issn.2095-428X.2018.13.009","article-title":"Effect of endogenous sulfur dioxide on the apoptosis induced by cobalt chloride in the human pulmonary arterial endothelial cells.","volume":"33","author":"Liu","year":"2018","journal-title":"Chin. J. Appl. Clin. Pediatr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bbrc.2011.10.012","article-title":"Endogenous generation of sulfur dioxide in rat tissues.","volume":"415","author":"Luo","year":"2011","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/aps.2012.70","article-title":"Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis.","volume":"33","author":"Ma","year":"2012","journal-title":"Acta Pharmacol. Sin"},{"key":"B26","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1097\/01.shk.0000183393.83272.de","article-title":"Oxidative stress-dependent conversion of hydrogen sulfide to sulfite by activated neutrophils.","volume":"24","author":"Mitsuhashi","year":"2005","journal-title":"Shock"},{"key":"B27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neulet.2017.11.036","article-title":"Endogenous sulfur dioxide regulates hippocampal neuron apoptosis in developing epileptic rats and is associated with the PERK signaling pathway.","volume":"665","author":"Niu","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2013.0852","article-title":"Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding.","volume":"11","author":"Qiu","year":"2013","journal-title":"J. R. Soc. Interface"},{"key":"B29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0165-1110(77)90020-3","article-title":"Genetic effects of bisulfite (sulfur dioxide).","volume":"39","author":"Shapiro","year":"1977","journal-title":"Mutat. Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/0003-9861(56)90363-0","article-title":"Intermediary metabolism of L-cysteinesulfinic acid in animal tissues.","volume":"61","author":"Singer","year":"1956","journal-title":"Arch. Biochem. Biophys."},{"key":"B31","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1146\/annurev.nutr.24.012003.132418","article-title":"Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine.","volume":"24","author":"Stipanuk","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1007\/s00018-020-03738-x","article-title":"Contribution of cell death signaling to blood vessel formation.","volume":"78","author":"Tisch","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1126\/science.1071553","article-title":"The Fas signaling pathway: more than a paradigm.","volume":"296","author":"Wajant","year":"2002","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00559","article-title":"SO2 donors and prodrugs, and their possible applications: a review.","volume":"6","author":"Wang","year":"2018","journal-title":"Front. Chem"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.14670\/HH-18-007","article-title":"Sulfur dioxide ameliorates rat myocardial fibrosis by inhibiting endoplasmic reticulum stress.","volume":"33","author":"Wang","year":"2018","journal-title":"Histol. Histopathol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1007\/s00395-011-0176-x","article-title":"Effect of sulfur dioxide preconditioning on rat myocardial ischemia\/reperfusion injury by inducing endoplasmic reticulum stress.","volume":"106","author":"Wang","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.preteyeres.2004.08.002","article-title":"Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration.","volume":"24","author":"Wenzel","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.niox.2018.09.005","article-title":"Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats.","volume":"81","author":"Yang","year":"2018","journal-title":"Nitric Oxide"},{"key":"B39","doi-asserted-by":"publisher","first-page":"998","DOI":"10.22038\/IJBMS.2018.29404.7106","article-title":"Sulfur dioxide reduces hippocampal cell death and improves learning and memory deficits in a rat model of transient global ischemia\/reperfusion.","volume":"21","author":"Zare Mehrjerdi","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/aps.2012.204","article-title":"The PI3K\/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia\/reperfusion injury in rats.","volume":"34","author":"Zhao","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.3321\/j.issn:0376-2491.2008.18.011","article-title":"Effects of sulfur dioxide, on the proliferation and apoptosis of aorta smooth muscle cells in hypertension: experiments with rats.","volume":"88","author":"Zhao","year":"2008","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B42","doi-asserted-by":"publisher","first-page":"239","DOI":"10.19723\/j.issn.1671-167X.2019.02.007","article-title":"Effects of sulfur dioxide on alveolar macrophage apoptosis in acute lung injury induced by limb ischemia\/reperfusion in rats.","volume":"51","author":"Zhao","year":"2019","journal-title":"J. Peking Univ"},{"key":"B43","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s12576-015-0418-z","article-title":"The PI3K\/Akt, p38MAPK, and JAK2\/STAT3 signaling pathways mediate the protection of SO2 against acute lung injury induced by limb ischemia\/reperfusion in rats.","volume":"66","author":"Zhao","year":"2016","journal-title":"J. Physiol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1097\/FJC.0000000000000882","article-title":"Sulfur dioxide: an endogenous protector against myocardial injury.","volume":"76","author":"Zhou","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.729728\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T11:26:40Z","timestamp":1633692400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.729728\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":44,"alternative-id":["10.3389\/fcell.2021.729728"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.729728","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]},"article-number":"729728"}}