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Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway
Ischemia/reperfusion (I/R) injury reduces cell proliferation, triggers inflammation, promotes cell apoptosis and necrosis, which are the leading reasons of morbidity and mortality in patients with cardiac disease. TGR5 is shown to express in hearts, but its functional role in I/R-induced myocardial...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981096/ https://www.ncbi.nlm.nih.gov/pubmed/31909787 http://dx.doi.org/10.1042/BSR20193482 |
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author | Li, Junzhi Cheng, Ruining Wan, Hong |
author_facet | Li, Junzhi Cheng, Ruining Wan, Hong |
author_sort | Li, Junzhi |
collection | PubMed |
description | Ischemia/reperfusion (I/R) injury reduces cell proliferation, triggers inflammation, promotes cell apoptosis and necrosis, which are the leading reasons of morbidity and mortality in patients with cardiac disease. TGR5 is shown to express in hearts, but its functional role in I/R-induced myocardial injury is unclear. In the present study, we aimed to explore the underlying molecular mechanism of TGR5 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro. The results showed that TGR5 was significantly up-regulated in H9C2 (rat cardiomyocyte cells) and human cardiomyocytes (HCMs) after H/R. Overexpression of TGR5 significantly improved cell proliferation, alleviated apoptosis rate, the activities of caspase-3, cleaved caspases-3 and Bax protein expression levels, and increased Bcl-2 level. Overexpression of TGR5 significantly up-regulated ROS generation, stabilized the mitochondrial membrane potential (MMP), and reduced the concentration of intracellular Ca(2+) as well as cytosolic translocation of mitochondrial cytochrome c (cyto-c). Meanwhile, overexpressed TGR5 also enhanced the mRNA and protein levels of interleukin (IL)-10, and decreased the mRNA and protein levels of IL-6 and tumor necrosis factor α (TNF-α). The shTGR5+H/R group followed opposite trends. In addition, overexpressed TGR5 induced an increase in the levels of p-AKT and p-GSK-3β. The protective effects of TGR5 were partially reversed by AKT inhibitor MK-2206. Taken together, these results suggest that TGR5 attenuates I/R-induced mitochondrial dysfunction and cell apoptosis as well as inflammation, and these protections may through AKT/GSK-3β pathway. |
format | Online Article Text |
id | pubmed-6981096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69810962020-02-05 Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway Li, Junzhi Cheng, Ruining Wan, Hong Biosci Rep Cell Death & Injury Ischemia/reperfusion (I/R) injury reduces cell proliferation, triggers inflammation, promotes cell apoptosis and necrosis, which are the leading reasons of morbidity and mortality in patients with cardiac disease. TGR5 is shown to express in hearts, but its functional role in I/R-induced myocardial injury is unclear. In the present study, we aimed to explore the underlying molecular mechanism of TGR5 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro. The results showed that TGR5 was significantly up-regulated in H9C2 (rat cardiomyocyte cells) and human cardiomyocytes (HCMs) after H/R. Overexpression of TGR5 significantly improved cell proliferation, alleviated apoptosis rate, the activities of caspase-3, cleaved caspases-3 and Bax protein expression levels, and increased Bcl-2 level. Overexpression of TGR5 significantly up-regulated ROS generation, stabilized the mitochondrial membrane potential (MMP), and reduced the concentration of intracellular Ca(2+) as well as cytosolic translocation of mitochondrial cytochrome c (cyto-c). Meanwhile, overexpressed TGR5 also enhanced the mRNA and protein levels of interleukin (IL)-10, and decreased the mRNA and protein levels of IL-6 and tumor necrosis factor α (TNF-α). The shTGR5+H/R group followed opposite trends. In addition, overexpressed TGR5 induced an increase in the levels of p-AKT and p-GSK-3β. The protective effects of TGR5 were partially reversed by AKT inhibitor MK-2206. Taken together, these results suggest that TGR5 attenuates I/R-induced mitochondrial dysfunction and cell apoptosis as well as inflammation, and these protections may through AKT/GSK-3β pathway. Portland Press Ltd. 2020-01-24 /pmc/articles/PMC6981096/ /pubmed/31909787 http://dx.doi.org/10.1042/BSR20193482 Text en © 2020 The Author(s). https://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). |
spellingShingle | Cell Death & Injury Li, Junzhi Cheng, Ruining Wan, Hong Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title | Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title_full | Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title_fullStr | Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title_full_unstemmed | Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title_short | Overexpression of TGR5 alleviates myocardial ischemia/reperfusion injury via AKT/GSK-3β mediated inflammation and mitochondrial pathway |
title_sort | overexpression of tgr5 alleviates myocardial ischemia/reperfusion injury via akt/gsk-3β mediated inflammation and mitochondrial pathway |
topic | Cell Death & Injury |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981096/ https://www.ncbi.nlm.nih.gov/pubmed/31909787 http://dx.doi.org/10.1042/BSR20193482 |
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