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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

Impact of 9-Phe on the size of myocardial infarction.Rats received a bolus injection of DMSO (control) or 9-Phe before (preconditioning) or after (postconditioning) ischemia during an ischemia/reperfusion (I/R) protocol. (A) Impact on the percentage of area at risk (AAR) caused by I/R. (B) Impact on the percent infarct size over AAR. A fixed detection threshold for infarcted area was arbitrarily set, and used throughout the analysis. Only 9-Phe preconditioning significantly reduced the percent infarcted size, compared to DMSO (n = 5–6; p < 0.01). (C) Typical TTC-stained heart slices after preconditioning with DMSO or 9-Phe. The blue region indicates cardiac tissue that received normal blood flow, whereas the red region indicates ischemic tissue due to LAD occlusion. The light red region encircled by a dotted line indicates the infarcted tissue.
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pone.0121703.g002: Impact of 9-Phe on the size of myocardial infarction.Rats received a bolus injection of DMSO (control) or 9-Phe before (preconditioning) or after (postconditioning) ischemia during an ischemia/reperfusion (I/R) protocol. (A) Impact on the percentage of area at risk (AAR) caused by I/R. (B) Impact on the percent infarct size over AAR. A fixed detection threshold for infarcted area was arbitrarily set, and used throughout the analysis. Only 9-Phe preconditioning significantly reduced the percent infarcted size, compared to DMSO (n = 5–6; p < 0.01). (C) Typical TTC-stained heart slices after preconditioning with DMSO or 9-Phe. The blue region indicates cardiac tissue that received normal blood flow, whereas the red region indicates ischemic tissue due to LAD occlusion. The light red region encircled by a dotted line indicates the infarcted tissue.

Mentions: Animal studies were conducted to determine whether 9-Phe may protect the heart against I/R injury. Successful ischemic treatment by LAD occlusion was confirmed by Evans blue staining at the end of each experiment. 9-Phe preconditioning did not significantly affect the size of AAR compared with DMSO preconditioning (34.8 ± 2.6% and 35.1 ± 3.1%, respectively; Fig 2A). In contrast, 9-Phe preconditioning significantly reduced myocardial infarct size (% infarcted area over AAR) (Fig 2B and 2C). The infarcted region was 4-fold smaller in the 9-Phe group than in the DMSO group (9.2 ± 1.1% and 37.5 ± 7.6%, respectively; p < 0.01).


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)

Impact of 9-Phe on the size of myocardial infarction.Rats received a bolus injection of DMSO (control) or 9-Phe before (preconditioning) or after (postconditioning) ischemia during an ischemia/reperfusion (I/R) protocol. (A) Impact on the percentage of area at risk (AAR) caused by I/R. (B) Impact on the percent infarct size over AAR. A fixed detection threshold for infarcted area was arbitrarily set, and used throughout the analysis. Only 9-Phe preconditioning significantly reduced the percent infarcted size, compared to DMSO (n = 5–6; p < 0.01). (C) Typical TTC-stained heart slices after preconditioning with DMSO or 9-Phe. The blue region indicates cardiac tissue that received normal blood flow, whereas the red region indicates ischemic tissue due to LAD occlusion. The light red region encircled by a dotted line indicates the infarcted tissue.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383534&req=5

pone.0121703.g002: Impact of 9-Phe on the size of myocardial infarction.Rats received a bolus injection of DMSO (control) or 9-Phe before (preconditioning) or after (postconditioning) ischemia during an ischemia/reperfusion (I/R) protocol. (A) Impact on the percentage of area at risk (AAR) caused by I/R. (B) Impact on the percent infarct size over AAR. A fixed detection threshold for infarcted area was arbitrarily set, and used throughout the analysis. Only 9-Phe preconditioning significantly reduced the percent infarcted size, compared to DMSO (n = 5–6; p < 0.01). (C) Typical TTC-stained heart slices after preconditioning with DMSO or 9-Phe. The blue region indicates cardiac tissue that received normal blood flow, whereas the red region indicates ischemic tissue due to LAD occlusion. The light red region encircled by a dotted line indicates the infarcted tissue.
Mentions: Animal studies were conducted to determine whether 9-Phe may protect the heart against I/R injury. Successful ischemic treatment by LAD occlusion was confirmed by Evans blue staining at the end of each experiment. 9-Phe preconditioning did not significantly affect the size of AAR compared with DMSO preconditioning (34.8 ± 2.6% and 35.1 ± 3.1%, respectively; Fig 2A). In contrast, 9-Phe preconditioning significantly reduced myocardial infarct size (% infarcted area over AAR) (Fig 2B and 2C). The infarcted region was 4-fold smaller in the 9-Phe group than in the DMSO group (9.2 ± 1.1% and 37.5 ± 7.6%, respectively; p < 0.01).

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