Transient receptor potential melastatin-4 is involved in hypoxia-reoxygenation injury in the cardiomyocytes

Hulin Piao, Ken Takahashi, Yohei Yamaguchi, Chen Wang, Kexiang Liu, Keiji Naruse

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Ischemic heart disease still remains the most common cause of cardiac death. During is-chemia-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 μ MH2O2 and hypoxia-reoxygenation. Gene silencing of TRPM4 preserved the viability of H9c2 cardiomyocytes exposed to 200 μMH2O2. These results suggest that the cardioprotective effects of 9-Phe are mediated through the inhibition of the TRPM4 channels.

Original languageEnglish
Article numbere0121703
JournalPLoS One
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 2 2015

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Cardiac Myocytes
hypoxia
reactive oxygen species
receptors
cell death
Wounds and Injuries
Reactive Oxygen Species
heart
cardioprotective effect
Cell death
Reperfusion Injury
infarction
myocardial infarction
rats
Reperfusion
gene silencing
Rats
myocardial ischemia
Cell Death
myocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transient receptor potential melastatin-4 is involved in hypoxia-reoxygenation injury in the cardiomyocytes. / Piao, Hulin; Takahashi, Ken; Yamaguchi, Yohei; Wang, Chen; Liu, Kexiang; Naruse, Keiji.

In: PLoS One, Vol. 10, No. 4, e0121703, 02.04.2015.

Research output: Contribution to journalArticle

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