Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 106, Issue 5, Pages 865-878Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-011-0176-x
Keywords
Sulfur dioxide; Preconditioning; Ischemia reperfusion; Endoplasmic reticulum stress
Categories
Funding
- National Natural Science Foundation of China [30821001, 81070111, 81070212]
- Changjiang Scholar Program
- Ministry of Education, China [20070001770, 307001, 20070001702]
- Major Basic Research Program of China [2011CB503904]
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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.
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