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 - Funding Information:
The authors are very grateful to Ms. Asami Okazaki (Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University) for her technical assistance with the MTT assay. The authors also wish to thank Ms. Yumiko Morishita (Central Research Laboratory, Okayama University Medical School) for her technical assistance with the histological preparations and staining. The work of Hulin Piao was supported by a scholarship from the China Scholarship Council. This work was funded by Grant-in-Aid for Strategic Research Promotion by the Okayama University.
Publisher Copyright:
© 2015 Piao et al.
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 -