Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783276354550104064 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5672082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangying attenuationofmir34aprotectscardiomyocytesagainsthypoxicstressthroughmaintenanceofglycolysis AT liugang attenuationofmir34aprotectscardiomyocytesagainsthypoxicstressthroughmaintenanceofglycolysis AT gaoxiaogang attenuationofmir34aprotectscardiomyocytesagainsthypoxicstressthroughmaintenanceofglycolysis |