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Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis

MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. MiR-34a is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclea...

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Detalles Bibliográficos
Autores principales: Zhang, Ying, Liu, Gang, Gao, Xiaogang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672082/
https://www.ncbi.nlm.nih.gov/pubmed/28894025
http://dx.doi.org/10.1042/BSR20170925
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author Zhang, Ying
Liu, Gang
Gao, Xiaogang
author_facet Zhang, Ying
Liu, Gang
Gao, Xiaogang
author_sort Zhang, Ying
collection PubMed
description MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. MiR-34a is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In the present study, we demonstrate that under low glucose supply, rat cardiomyocytes are susceptible to hypoxia. Under short-time hypoxia, cellular glucose uptake and lactate product are induced but under long-time hypoxia, the cellular glucose metabolism is suppressed. Interestingly, an adaptive up-regulation of miR-34a by long-time hypoxia was observed both in vitro and in vivo, leading to suppression of glycolysis in cardiomyocytes. We identified lactate dehydrogenase-A (LDHA) as a direct target of miR-34a, which binds to the 3′-UTR region of LDHA mRNA in cardiomyocytes. Moreover, inhibition of miR-34a attenuated hypoxia-induced cardiomyocytes dysfunction through restoration of glycolysis. The present study illustrates roles of miR-34a in the hypoxia-induced cardiomyocytes dysfunction and proposes restoration of glycolysis of dysfunctional cardiomyocytes by inhibiting miR-34a during I/R might be an effectively therapeutic approach against I/R injury.
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spelling pubmed-56720822017-11-07 Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis Zhang, Ying Liu, Gang Gao, Xiaogang Biosci Rep Research Articles MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. MiR-34a is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In the present study, we demonstrate that under low glucose supply, rat cardiomyocytes are susceptible to hypoxia. Under short-time hypoxia, cellular glucose uptake and lactate product are induced but under long-time hypoxia, the cellular glucose metabolism is suppressed. Interestingly, an adaptive up-regulation of miR-34a by long-time hypoxia was observed both in vitro and in vivo, leading to suppression of glycolysis in cardiomyocytes. We identified lactate dehydrogenase-A (LDHA) as a direct target of miR-34a, which binds to the 3′-UTR region of LDHA mRNA in cardiomyocytes. Moreover, inhibition of miR-34a attenuated hypoxia-induced cardiomyocytes dysfunction through restoration of glycolysis. The present study illustrates roles of miR-34a in the hypoxia-induced cardiomyocytes dysfunction and proposes restoration of glycolysis of dysfunctional cardiomyocytes by inhibiting miR-34a during I/R might be an effectively therapeutic approach against I/R injury. Portland Press Ltd. 2017-11-06 /pmc/articles/PMC5672082/ /pubmed/28894025 http://dx.doi.org/10.1042/BSR20170925 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Zhang, Ying
Liu, Gang
Gao, Xiaogang
Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title_full Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title_fullStr Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title_full_unstemmed Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title_short Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
title_sort attenuation of mir-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672082/
https://www.ncbi.nlm.nih.gov/pubmed/28894025
http://dx.doi.org/10.1042/BSR20170925
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