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 language | English |
|---|---|
| Article number | e0121703 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2 2015 |
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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 journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84926483181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926483181&partnerID=8YFLogxK
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 -