title: Effect of sulfur dioxide preconditioning on rat myocardial ischemia/reperfusion injury by inducing endoplasmic reticulum stress.
abstract: Sulfur dioxide has recently been found to be produced endogenously in the cardiovascular system and have important positive biological effects. However, it is unknown whether sulfur dioxide preconditioning has a protective effect on rat myocardial ischemia/reperfusion (I/R) injury and whether this process involves endoplasmic reticulum stress (ERS). In this study, we showed that preconditioning with sulfur dioxide 10 min before ischemia (with a low concentration of sulfur dioxide of 1-10 μmol/kg) could reduce myocardial infarct size and plasma activities of lactate dehydrogenase and creatine kinase in rats with I/R in vivo. Sulfur dioxide preconditioning also reduced myocardium apoptosis induced by I/R. In addition, sulfur dioxide preconditioning increased cardiac function in vitro. Sulfur dioxide preconditioning induced expression of myocardial glucose-regulated protein 78 (GRP78) and phosphorylated eukaryotic initiation of the factor 2α-subunit (p-eIF2α) prior to myocardial I/R but suppressed expression of myocardial GRP78, C/EBP homologous protein, and p-eIF2α during myocardial I/R, in association with improved myocardial injury in vivo and in vitro. Pretreatment with dithiothreitol, an ERS stimulator mimicked the above cardioprotective effect. However, pretreatment with the ERS inhibitor 4-phenylbutyrate reversed the cardioprotection provided by sulfur dioxide preconditioning. These data indicated that sulfur dioxide preconditioning reduced I/R-induced myocardial injury in vivo and in vitro, and that augmenting ERS by sulfur dioxide preconditioning prior to I/R contributed to protection against myocardial I/R injury.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xin-Bao
authors.initials: XB
authors.lastname: Wang
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Huang
authors.forename: Todd
authors.initials: T
authors.lastname: Ochs
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Jin
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Jun-Bao
authors.initials: JB
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053454:Caspase 12 / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004229:Dithiothreitol / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D010654:Phenylbutyrates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D013458:Sulfur Dioxide / Q000378:metabolism / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D003402:Creatine Kinase; D004229:Dithiothreitol; D006360:Heat-Shock Proteins; D007770:L-Lactate Dehydrogenase; D010654:Phenylbutyrates; D013458:Sulfur Dioxide; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C075773:4-phenylbutyric acid; C506443:Casp12 protein, rat