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

Piao H, Takahashi K, Yamaguchi Y, Wang C, Liu K, Naruse K - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Animal experimental protocol.Rats were treated with the vehicle (DMSO; Groups 1 and 3) or 9-Phe (1 mg/kg in DMSO; Groups 2 and 4). The bolus injections into the jugular vein were given before (preconditioning; Groups 1 and 2) or after (postconditioning; Groups 3 and 4) ischemia. The 30-min ischemia period was followed by 120 min of reperfusion, and then the hearts were collected for TTC staining.
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pone.0121703.g001: Animal experimental protocol.Rats were treated with the vehicle (DMSO; Groups 1 and 3) or 9-Phe (1 mg/kg in DMSO; Groups 2 and 4). The bolus injections into the jugular vein were given before (preconditioning; Groups 1 and 2) or after (postconditioning; Groups 3 and 4) ischemia. The 30-min ischemia period was followed by 120 min of reperfusion, and then the hearts were collected for TTC staining.

Mentions: The rats were randomly divided into four groups. Group 1 and Group 3 were administered dimethyl sulfoxide (DMSO), whereas Group 2 and Group 4 were administered 9-Phe (1 mg/kg; dissolved in DMSO). All treatments were single intravenous bolus injections into the jugular vein. Whereas Groups 1 and 2 were treated 20 min before ischemia (preconditioning), Groups 3 and 4 were treated at the onset of reperfusion (postconditioning; Fig 1).


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

Piao H, Takahashi K, Yamaguchi Y, Wang C, Liu K, Naruse K - PLoS ONE (2015)

Animal experimental protocol.Rats were treated with the vehicle (DMSO; Groups 1 and 3) or 9-Phe (1 mg/kg in DMSO; Groups 2 and 4). The bolus injections into the jugular vein were given before (preconditioning; Groups 1 and 2) or after (postconditioning; Groups 3 and 4) ischemia. The 30-min ischemia period was followed by 120 min of reperfusion, and then the hearts were collected for TTC staining.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383534&req=5

pone.0121703.g001: Animal experimental protocol.Rats were treated with the vehicle (DMSO; Groups 1 and 3) or 9-Phe (1 mg/kg in DMSO; Groups 2 and 4). The bolus injections into the jugular vein were given before (preconditioning; Groups 1 and 2) or after (postconditioning; Groups 3 and 4) ischemia. The 30-min ischemia period was followed by 120 min of reperfusion, and then the hearts were collected for TTC staining.
Mentions: The rats were randomly divided into four groups. Group 1 and Group 3 were administered dimethyl sulfoxide (DMSO), whereas Group 2 and Group 4 were administered 9-Phe (1 mg/kg; dissolved in DMSO). All treatments were single intravenous bolus injections into the jugular vein. Whereas Groups 1 and 2 were treated 20 min before ischemia (preconditioning), Groups 3 and 4 were treated at the onset of reperfusion (postconditioning; Fig 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus