Transient Receptor Potential Melastatin-4 Is Involved in Hypoxia-Reoxygenation Injury in the Cardiomyocytes |
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| Authors: | Hulin Piao Ken Takahashi Yohei Yamaguchi Chen Wang Kexiang Liu Keiji Naruse |
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| Affiliation: | 1. Department of Cardiovascular Surgery, the Second Affiliated Hospital of Jilin University, Changchun, China.; 2. Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.; 3. Department of Cardiology, Graduate School, Dalian Medical University, Dalian, China.; Virginia Commonwealth University, UNITED STATES, |
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| Abstract: | Ischemic heart disease still remains the most common cause of cardiac death. During ischemia-reperfusion (I/R), reactive oxygen species (ROS) are produced in excess in cardiac tissue, where they induce cell death. Our previous study showed that 9-phenanthrol (9-Phe), a specific inhibitor of the TRPM4 channel, preserves cardiac contractile function and protects the heart from I/R injury-related infarction in the excised rat heart. Accordingly, we hypothesized that TRPM4 channels are involved in the 9-Phe-mediated cardioprotection against ROS-induced injury. In rats, intravenous 9-Phe mitigated the development of myocardial infarction caused by the occlusion of the left anterior descending artery. Immunohistochemical analysis indicated that TRPM4 proteins are expressed in ventricular myocytes susceptible to I/R injury. Hydrogen peroxide (H2O2) is among the main ROS overproduced during I/R. In the cardiomyocyte cell line H9c2, pretreatment with 9-Phe prevented cell death induced by conditions mimicking I/R, namely 200 μM H2O2 and hypoxia-reoxygenation. Gene silencing of TRPM4 preserved the viability of H9c2 cardiomyocytes exposed to 200 μM H2O2. These results suggest that the cardioprotective effects of 9-Phe are mediated through the inhibition of the TRPM4 channels. |
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