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

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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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (30821001, 81070111 to J. -B. Du, 81070212 to H. -F. Jin), the Changjiang Scholar Program, and grants from the Ministry of Education, China (20070001770, 307001 and 20070001702 to J. -B. Du) and the Major Basic Research Program of China (2011CB503904 to J. -B. Du).

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China

    Xin-Bao Wang, Xiao-Mei Huang, Hong-Fang Jin & Jun-Bao Du

  2. University of Illinois School of Medicine, Chicago, USA

    Todd Ochs

  3. Department of Statistics, Peking University First Hospital, Beijing, 100034, China

    Xue-Ying Li

  4. Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, 100191, China

    Chao-Shu Tang

  5. Department of Physiology and Pathophysiology, Health Science Center Peking University, Beijing, 100191, China

    Chao-Shu Tang

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  1. Xin-Bao Wang
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  2. Xiao-Mei Huang
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  4. Xue-Ying Li
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  5. Hong-Fang Jin
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Correspondence to Hong-Fang Jin or Jun-Bao Du.

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X.-B. Wang and X.-M. Huang are co-first authors, contributed equally to this work.

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Wang, XB., Huang, XM., Ochs, T. et al. Effect of sulfur dioxide preconditioning on rat myocardial ischemia/reperfusion injury by inducing endoplasmic reticulum stress. Basic Res Cardiol 106, 865–878 (2011). https://doi.org/10.1007/s00395-011-0176-x

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