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Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice

BACKGROUND: Resveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothe...

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Autores principales: Du, Ren-Hong, Dai, Ting, Cao, Wen-Jing, Lu, Ming, Ding, Jian-hua, Hu, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916794/
https://www.ncbi.nlm.nih.gov/pubmed/24498880
http://dx.doi.org/10.1186/1475-2840-13-35
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author Du, Ren-Hong
Dai, Ting
Cao, Wen-Jing
Lu, Ming
Ding, Jian-hua
Hu, Gang
author_facet Du, Ren-Hong
Dai, Ting
Cao, Wen-Jing
Lu, Ming
Ding, Jian-hua
Hu, Gang
author_sort Du, Ren-Hong
collection PubMed
description BACKGROUND: Resveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol. METHODS: Kir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection. RESULTS: Resveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation – induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5′-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator. CONCLUSIONS: Our study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol.
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spelling pubmed-39167942014-02-08 Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice Du, Ren-Hong Dai, Ting Cao, Wen-Jing Lu, Ming Ding, Jian-hua Hu, Gang Cardiovasc Diabetol Original Investigation BACKGROUND: Resveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol. METHODS: Kir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection. RESULTS: Resveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation – induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5′-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator. CONCLUSIONS: Our study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol. BioMed Central 2014-02-05 /pmc/articles/PMC3916794/ /pubmed/24498880 http://dx.doi.org/10.1186/1475-2840-13-35 Text en Copyright © 2014 Du et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Du, Ren-Hong
Dai, Ting
Cao, Wen-Jing
Lu, Ming
Ding, Jian-hua
Hu, Gang
Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title_full Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title_fullStr Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title_full_unstemmed Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title_short Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice
title_sort kir6.2-containing atp-sensitive k(+) channel is required for cardioprotection of resveratrol in mice
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916794/
https://www.ncbi.nlm.nih.gov/pubmed/24498880
http://dx.doi.org/10.1186/1475-2840-13-35
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