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: Xin-Bao Wang, Xiao-Mei Huang, Todd Ochs, Xue-Ying Li, Hong-Fang Jin, Chao-Shu Tang, Jun-Bao Du
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 106 Issue 5 Pg. 865-78 (Sep 2011) ISSN: 1435-1803 [Electronic] Germany
• PMID: 21468766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ddit3 protein, rat
• GRP78 protein, rat
• Heat-Shock Proteins
• Phenylbutyrates
• Sulfur Dioxide
• Transcription Factor CHOP
• 4-phenylbutyric acid
• L-Lactate Dehydrogenase
• Creatine Kinase
• Casp12 protein, rat
• Caspase 12
• Dithiothreitol

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Caspase 12 (metabolism)
• Creatine Kinase (blood)
• Dithiothreitol (pharmacology)
• Endoplasmic Reticulum (drug effects, physiology)
• Heart (drug effects, physiology)
• Heat-Shock Proteins (metabolism)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• L-Lactate Dehydrogenase (blood)
• Male
• Models, Animal
• Myocardial Infarction (metabolism, pathology)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Phenylbutyrates (pharmacology)
• Rats
• Rats, Wistar
• Stress, Physiological (drug effects, physiology)
• Sulfur Dioxide (metabolism, pharmacology)
• Transcription Factor CHOP (metabolism)