TY - JOUR
T1 - Transient receptor potential melastatin-4 is involved in hypoxia-reoxygenation injury in the cardiomyocytes
AU - Piao, Hulin
AU - Takahashi, Ken
AU - Yamaguchi, Yohei
AU - Wang, Chen
AU - Liu, Kexiang
AU - Naruse, Keiji
N1 - Publisher Copyright:
© 2015 Piao et al.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/4/2
Y1 - 2015/4/2
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0121703
DO - 10.1371/journal.pone.0121703
M3 - Article
C2 - 25836769
AN - SCOPUS:84926483181
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0121703
ER -