title: Transient receptor potential melastatin-4 is involved in hypoxia-reoxygenation injury in the cardiomyocytes.
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.
authors.affiliation: Department of Cardiovascular Surgery, the Second Affiliated Hospital of Jilin University, Changchun, China; Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Hulin
authors.initials: H
authors.lastname: Piao
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Cardiology, Graduate School, Dalian Medical University, Dalian, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, the Second Affiliated Hospital of Jilin University, Changchun, China.
authors.forename: Kexiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D010616:Phenanthrenes / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C500239:TRPM4 protein, rat; C091375:9-phenanthrol; D006861:Hydrogen Peroxide
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