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Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission

In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 car...

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Autores principales: Tian, Yanan, Song, Haijiu, Qin, Wei, Ding, Zhenjiang, Zhang, Ying, Shan, Weichao, Jin, Dapeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424023/
https://www.ncbi.nlm.nih.gov/pubmed/32848850
http://dx.doi.org/10.3389/fphys.2020.00897
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author Tian, Yanan
Song, Haijiu
Qin, Wei
Ding, Zhenjiang
Zhang, Ying
Shan, Weichao
Jin, Dapeng
author_facet Tian, Yanan
Song, Haijiu
Qin, Wei
Ding, Zhenjiang
Zhang, Ying
Shan, Weichao
Jin, Dapeng
author_sort Tian, Yanan
collection PubMed
description In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 cardiomyocytes. LPS treatment induced expression of IL-2, IL-8, and MMP9 mRNA and proteins in the H9C2 cardiomyocytes, and this was accompanied by increased caspase-3/9 mediating H9C2 cardiomyocyte apoptosis. LPS treatment also increased mitochondrial reactive oxygen species (ROS) and the levels of antioxidant enzymes, such as GSH, SOD, and GPX, in the H9C2 cardiomyocytes. The LPS-treated H9C2 cardiomyocytes showed lower cellular ATP levels and mitochondrial state-3/4 respiration but increased mitochondrial fragmentation, including upregulation of the mitochondrial fission genes Drp1, Mff, and Fis1. LPS-induced inflammation, mitochondrial ROS, mitochondrial fission, and apoptosis were all significantly suppressed by pre-treating the H9C2 cardiomyocytes with the Mst2 inhibitor, XMU-MP1. However, the beneficial effects of Mst2 inhibition by XMU-MP1 were abolished by carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), a potent activator of mitochondrial fission. These findings demonstrate that Mst2 mediates LPS-induced cardiomyocyte inflammation and apoptosis by increasing mitochondrial fission.
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spelling pubmed-74240232020-08-25 Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission Tian, Yanan Song, Haijiu Qin, Wei Ding, Zhenjiang Zhang, Ying Shan, Weichao Jin, Dapeng Front Physiol Physiology In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 cardiomyocytes. LPS treatment induced expression of IL-2, IL-8, and MMP9 mRNA and proteins in the H9C2 cardiomyocytes, and this was accompanied by increased caspase-3/9 mediating H9C2 cardiomyocyte apoptosis. LPS treatment also increased mitochondrial reactive oxygen species (ROS) and the levels of antioxidant enzymes, such as GSH, SOD, and GPX, in the H9C2 cardiomyocytes. The LPS-treated H9C2 cardiomyocytes showed lower cellular ATP levels and mitochondrial state-3/4 respiration but increased mitochondrial fragmentation, including upregulation of the mitochondrial fission genes Drp1, Mff, and Fis1. LPS-induced inflammation, mitochondrial ROS, mitochondrial fission, and apoptosis were all significantly suppressed by pre-treating the H9C2 cardiomyocytes with the Mst2 inhibitor, XMU-MP1. However, the beneficial effects of Mst2 inhibition by XMU-MP1 were abolished by carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), a potent activator of mitochondrial fission. These findings demonstrate that Mst2 mediates LPS-induced cardiomyocyte inflammation and apoptosis by increasing mitochondrial fission. Frontiers Media S.A. 2020-08-06 /pmc/articles/PMC7424023/ /pubmed/32848850 http://dx.doi.org/10.3389/fphys.2020.00897 Text en Copyright © 2020 Tian, Song, Qin, Ding, Zhang, Shan and Jin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Tian, Yanan
Song, Haijiu
Qin, Wei
Ding, Zhenjiang
Zhang, Ying
Shan, Weichao
Jin, Dapeng
Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title_full Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title_fullStr Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title_full_unstemmed Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title_short Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission
title_sort mammalian ste20-like kinase 2 promotes lipopolysaccharides-mediated cardiomyocyte inflammation and apoptosis by enhancing mitochondrial fission
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424023/
https://www.ncbi.nlm.nih.gov/pubmed/32848850
http://dx.doi.org/10.3389/fphys.2020.00897
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