{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:25:11Z","timestamp":1773307511317,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T00:00:00Z","timestamp":1383868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemia\/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia\/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO2) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1\/2 (ERK1\/2) signaling pathway mediated protection against cardiac dysfunction after  SO2 preconditioning in isolated rat hearts subjected to ischemia\/reperfusion (I\/R).  Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 \u03bcmol\/L SO2 group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) + 5 \u03bcmol\/L SO2 (PD98059 + S5) group, PD98059 group, I\/R group, 5 \u03bcmol\/L SO2 + I\/R (S5 + I\/R) group and PD98059 + 5 \u03bcmol\/L SO2 + I\/R (PD98059 + S5 + I\/R) group. Cardiac function and myocardial phosphorylated ERK1\/2 protein were measured. We found that I\/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1\/2 protein. SO2 preconditioning markedly suppressed phosphorylated ERK1\/2 protein and improved cardiac function in isolated rat heart with I\/R (p &lt; 0.05). However, pre-treatment with PD98059 could prevent the above effects of SO2 preconditioning. In conclusion, SO2 preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I\/R via suppression of the over-activation of the ERK1\/2 signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms141122190","type":"journal-article","created":{"date-parts":[[2013,11,11]],"date-time":"2013-11-11T03:21:37Z","timestamp":1384140097000},"page":"22190-22201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The ERK1\/2 Signaling Pathway Is Involved in Sulfur Dioxide Preconditioning-Induced Protection against Cardiac Dysfunction in Isolated Perfused Rat Heart Subjected to Myocardial Ischemia\/Reperfusion"],"prefix":"10.3390","volume":"14","author":[{"given":"Pan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Sciences, Link\u00f6ping University, Link\u00f6ping 58183, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Holmberg","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Sciences, Link\u00f6ping University, Link\u00f6ping 58183, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoshu","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"},{"name":"Department of Physiology and Pathophysiology, Health Sciences Center, Peking University,  Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"},{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China"},{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00395-009-0044-0","article-title":"Attenuation of myocardial injury by postconditioning: Role of hypoxia inducible factor-1\u03b1","volume":"105","author":"Zhao","year":"2010","journal-title":"Basic Res. Cardiol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jss.2012.04.069","article-title":"Early protective effect of total hypoxic preconditioning on rats against systemic injury from hemorrhagic shock and resuscitation","volume":"178","author":"Duan","year":"2012","journal-title":"J. Surg. Res"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1540-8183.2012.00747.x","article-title":"Pharmacologic preconditioning therapy prior to atrial septal defect closure in patients at high risk for acute pulmonary edema","volume":"25","author":"Gruner","year":"2012","journal-title":"J. Interv. Cardiol"},{"key":"ref_4","doi-asserted-by":"crossref","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":"2008","journal-title":"Acta Pharmacol. Sin"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1111\/j.1745-7254.2008.00864.x","article-title":"Effects of endogenous sulfur dioxide on monocrotaline-induced pulmonary hypertension in rats","volume":"29","author":"Jin","year":"2008","journal-title":"Acta Pharmacol. Sin"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/labinvest.2009.102","article-title":"Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling","volume":"90","author":"Sun","year":"2010","journal-title":"Lab. Invest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.niox.2008.12.003","article-title":"The role of sulfur dioxide as an endogenous gaseous vasoactive factor in synergy with nitric oxide","volume":"20","author":"Li","year":"2009","journal-title":"Nitric Oxide"},{"key":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1080\/08958370701515175","article-title":"The vasodilator effect and its mechanism of sulfur dioxide-derivatives on isolated aortic rings of rats","volume":"19","author":"Meng","year":"2007","journal-title":"Inhal. Toxicol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.33549\/physiolres.931456","article-title":"Sulfur dioxide relaxes rat aorta by endothelium-dependent and independent mechanisms","volume":"58","author":"Wang","year":"2009","journal-title":"Physiol. Res"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ejphar.2008.11.030","article-title":"The vasodilator mechanism of sulfur dioxide on isolated aortic rings of rats: Involvement of the K+ and Ca2+ channels","volume":"602","author":"Zhang","year":"2009","journal-title":"Eur. J. Pharmacol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/TP.0b013e318195fe82","article-title":"Endogenous sulfur dioxide aggravates myocardial injury in isolated rat heart with ischemia and reperfusion","volume":"87","author":"Zhang","year":"2009","journal-title":"Transplantation"},{"key":"ref_13","doi-asserted-by":"crossref","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":"ref_14","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1152\/physrev.1999.79.1.143","article-title":"Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human","volume":"79","author":"Widmann","year":"1999","journal-title":"Physiol. Rev"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11248-006-9052-0","article-title":"In vivo functions of mitogen-activated protein kinases: Conclusions from knock-in and knock-out mice","volume":"16","author":"Gerits","year":"2007","journal-title":"Transgenic Res"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13585","DOI":"10.1074\/jbc.270.23.13585","article-title":"Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor","volume":"270","author":"Pang","year":"1995","journal-title":"J. Biol. Chem"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.transproceed.2012.03.045","article-title":"Fractalkine increases mesangial cell proliferation through reactive oxygen species and mitogen-activated protein kinases","volume":"44","author":"Park","year":"2012","journal-title":"Transpl. Proc"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s12272-012-0417-z","article-title":"Anti-inflammatory effects of Z-ligustilide through suppression of mitogen-activated protein kinases and nuclear factor-\u03baB activation pathways","volume":"35","author":"Chung","year":"2012","journal-title":"Arch. Pharm. Res"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.tiv.2012.04.022","article-title":"Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-\u03baB and MAPK signaling pathways","volume":"26","author":"Himaya","year":"2012","journal-title":"Toxicol. Vitro"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/00006676-200308000-00008","article-title":"Pancreatic stellate cell activation by ethanol and acetaldehyde: Is it mediated by the mitogen-activated protein kinase signaling pathway?","volume":"27","author":"McCarroll","year":"2003","journal-title":"Pancreas"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1471-2172-13-28","article-title":"Ignification of decoy receptor 3 (DcR3) and external-signal regulated kinase 1\/2 (ERK1\/2) in gastric cancer patients","volume":"13","author":"Yang","year":"2012","journal-title":"BMC Immunol"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1213\/ANE.0b013e318232b35a","article-title":"Morphine-induced epidermal growth factor pathway activation in non-small cell lung cancer","volume":"113","author":"Fujioka","year":"2011","journal-title":"Anesth. Analg"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2010.09.053","article-title":"Inhibition of activated ERK1\/2 and JNKs improves vascular function in mouse aortae in the absence of nitric oxide","volume":"658","author":"Bhattacharya","year":"2011","journal-title":"Eur. J. Pharmacol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/bj3500891","article-title":"Sustained activation of p42\/p44 mitogen-activated protein kinase during recovery from simulated ischaemia mediates adaptive cytoprotection in cardiomyocytes","volume":"350","author":"Punn","year":"2000","journal-title":"Biochem. J"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1126\/science.1411546","article-title":"The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product","volume":"258","author":"Crews","year":"1992","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0092-8674(94)90133-3","article-title":"Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells","volume":"77","author":"Cowley","year":"1994","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7686","DOI":"10.1073\/pnas.92.17.7686","article-title":"A synthetic inhibitor of the mitogen-activated protein kinase cascade","volume":"92","author":"Dudley","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1002\/j.1460-2075.1994.tb06424.x","article-title":"Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1","volume":"13","author":"Alessi","year":"1994","journal-title":"EMBO J"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00395-010-0121-4","article-title":"Translating novel strategies for cardioprotection: The hatter workshop recommendations","volume":"105","author":"Hausenloy","year":"2010","journal-title":"Basic Res. Cardiol"},{"key":"ref_31","first-page":"77","article-title":"Angioplasty as early revascularization in acute myocardial infarction","volume":"8","author":"Koca","year":"2008","journal-title":"Anadolu. Kardiyol. Derg"},{"key":"ref_32","first-page":"84","article-title":"Surgery as early revascularization after acute myocardial infarction","volume":"8","author":"Yavuz","year":"2008","journal-title":"Anadolu. Kardiyol. Derg"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium","volume":"74","author":"Murry","year":"1986","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.tox.2005.08.016","article-title":"Expression of apoptosis-related genes in livers from rats exposed to sulfur dioxide","volume":"216","author":"Bai","year":"2005","journal-title":"Toxicology"},{"key":"ref_35","doi-asserted-by":"crossref","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":"311","author":"Balazy","year":"2003","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/01.RES.86.6.692","article-title":"Inhibition of extracellular signal-regulated kinase enhances ischemia\/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart","volume":"86","author":"Yue","year":"2000","journal-title":"Circ. Res"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1161\/01.CIR.0000127126.73759.23","article-title":"MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo","volume":"109","author":"Lips","year":"2004","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"H1236","DOI":"10.1152\/ajpheart.00100.2009","article-title":"ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice","volume":"296","author":"Das","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00395-011-0165-0","article-title":"Cardioprotection by mild hypothermia during ischemia involves preservation of ERK activity","volume":"106","author":"Yang","year":"2011","journal-title":"Basic Res. Cardiol"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00395-005-0569-9","article-title":"Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury\u2014Evidence for a role of KATP channels","volume":"101","author":"Johansen","year":"2006","journal-title":"Basic Res. Cardiol"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:29Z","timestamp":1760219429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,8]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11]]}},"alternative-id":["ijms141122190"],"URL":"https:\/\/doi.org\/10.3390\/ijms141122190","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,8]]}}}