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MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1

Dysfunction of cardiac cells under hypoxia has been identified as an essential event leading to myocytes functional failure. MiRNAs are importantly regulatory small-noncoding RNAs that negatively regulate gene expression through the direct binding of 3′-UTR region of their target mRNAs. Recent studi...

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Autores principales: Zhu, Hang, Xue, Hao, Jin, Qin-Hua, Guo, Jun, Chen, Yun-Dai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696451/
https://www.ncbi.nlm.nih.gov/pubmed/28899927
http://dx.doi.org/10.1042/BSR20170296
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author Zhu, Hang
Xue, Hao
Jin, Qin-Hua
Guo, Jun
Chen, Yun-Dai
author_facet Zhu, Hang
Xue, Hao
Jin, Qin-Hua
Guo, Jun
Chen, Yun-Dai
author_sort Zhu, Hang
collection PubMed
description Dysfunction of cardiac cells under hypoxia has been identified as an essential event leading to myocytes functional failure. MiRNAs are importantly regulatory small-noncoding RNAs that negatively regulate gene expression through the direct binding of 3′-UTR region of their target mRNAs. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under pathological conditions.Pyruvate dehydrogenase kinase 1 (PDK1) is a kinase which phosphorylates pyruvate dehydrogenase to inactivate it, leading to elevated anaerobic glycolysis and decreased cellular respiration. In the present study, we report that miR-138 expressions were significantly suppressed under long exposure to hypoxia. In addition, overexpression of miR-138 protects human cardiac cells against hypoxia. We observed miR-138 inhibits glycolysis but promotes mitochondrial respiration through directly targetting PDK1. Moreover, we demonstrate that hypoxia induces cardiac cell death through increased glycolysis and decreased mitochondrial respiration. Inhibition of glycolysis by either glycolysis inhibitor or knockdown glycolysis enzymes, Glucose transportor 1 (Glut1) or PDK1 contributes to cardiac cells’ survival. The cell sentivity to hypoxia was recovered when the PDK1 level was restored in miR-138 overexpressing cardiac cells. The present study leads to the intervention of novel therapeutic strategies against cardiac cells dysfunction during surgery or ischemia.
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spelling pubmed-56964512017-11-28 MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1 Zhu, Hang Xue, Hao Jin, Qin-Hua Guo, Jun Chen, Yun-Dai Biosci Rep Research Articles Dysfunction of cardiac cells under hypoxia has been identified as an essential event leading to myocytes functional failure. MiRNAs are importantly regulatory small-noncoding RNAs that negatively regulate gene expression through the direct binding of 3′-UTR region of their target mRNAs. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under pathological conditions.Pyruvate dehydrogenase kinase 1 (PDK1) is a kinase which phosphorylates pyruvate dehydrogenase to inactivate it, leading to elevated anaerobic glycolysis and decreased cellular respiration. In the present study, we report that miR-138 expressions were significantly suppressed under long exposure to hypoxia. In addition, overexpression of miR-138 protects human cardiac cells against hypoxia. We observed miR-138 inhibits glycolysis but promotes mitochondrial respiration through directly targetting PDK1. Moreover, we demonstrate that hypoxia induces cardiac cell death through increased glycolysis and decreased mitochondrial respiration. Inhibition of glycolysis by either glycolysis inhibitor or knockdown glycolysis enzymes, Glucose transportor 1 (Glut1) or PDK1 contributes to cardiac cells’ survival. The cell sentivity to hypoxia was recovered when the PDK1 level was restored in miR-138 overexpressing cardiac cells. The present study leads to the intervention of novel therapeutic strategies against cardiac cells dysfunction during surgery or ischemia. Portland Press Ltd. 2017-11-21 /pmc/articles/PMC5696451/ /pubmed/28899927 http://dx.doi.org/10.1042/BSR20170296 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
Zhu, Hang
Xue, Hao
Jin, Qin-Hua
Guo, Jun
Chen, Yun-Dai
MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title_full MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title_fullStr MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title_full_unstemmed MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title_short MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
title_sort mir-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696451/
https://www.ncbi.nlm.nih.gov/pubmed/28899927
http://dx.doi.org/10.1042/BSR20170296
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