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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2017
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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. |
format | Online Article Text |
id | pubmed-5696451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
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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