Effect of sulfur dioxide preconditioning on rat myocardial ischemia/reperfusion injury by inducing endoplasmic reticulum stress

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 mu mol/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 2 alpha-subunit (p-eIF2 alpha) prior to myocardial I/R but suppressed expression of myocardial GRP78, C/EBP homologous protein, and p-eIF2 alpha 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.