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Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State
BACKGROUND: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808370/ https://www.ncbi.nlm.nih.gov/pubmed/24204728 http://dx.doi.org/10.1371/journal.pone.0077034 |
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author | Dong, Ruolan Xu, Xizhen Li, Geng Feng, Wenjing Zhao, Gang Zhao, Junjie Wang, Dao Wen Tu, Ling |
author_facet | Dong, Ruolan Xu, Xizhen Li, Geng Feng, Wenjing Zhao, Gang Zhao, Junjie Wang, Dao Wen Tu, Ling |
author_sort | Dong, Ruolan |
collection | PubMed |
description | BACKGROUND: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK) protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H(2)O(2)-induced H9C2 cells senescence. METHODS AND RESULTS: Bradykinin pretreatment decreased the senescence induced by H(2)O(2) in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H(2)O(2). Since H(2)O(2) induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H(2)O(2), and moreover, BK treatment significantly prevented reactive oxygen species (ROS) production in H9C2 cells treated with H(2)O(2). Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME), the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD) activity and expression induced by H(2)O(2) in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO) release. CONCLUSIONS: Bradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while downregulating NADPH oxidase activity and subsequently inhibited ROS production, and finally protected against cardiomyocytes senescence induced by oxidative stress. |
format | Online Article Text |
id | pubmed-3808370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38083702013-11-07 Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State Dong, Ruolan Xu, Xizhen Li, Geng Feng, Wenjing Zhao, Gang Zhao, Junjie Wang, Dao Wen Tu, Ling PLoS One Research Article BACKGROUND: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK) protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H(2)O(2)-induced H9C2 cells senescence. METHODS AND RESULTS: Bradykinin pretreatment decreased the senescence induced by H(2)O(2) in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H(2)O(2). Since H(2)O(2) induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H(2)O(2), and moreover, BK treatment significantly prevented reactive oxygen species (ROS) production in H9C2 cells treated with H(2)O(2). Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME), the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD) activity and expression induced by H(2)O(2) in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO) release. CONCLUSIONS: Bradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while downregulating NADPH oxidase activity and subsequently inhibited ROS production, and finally protected against cardiomyocytes senescence induced by oxidative stress. Public Library of Science 2013-10-25 /pmc/articles/PMC3808370/ /pubmed/24204728 http://dx.doi.org/10.1371/journal.pone.0077034 Text en © 2013 Dong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dong, Ruolan Xu, Xizhen Li, Geng Feng, Wenjing Zhao, Gang Zhao, Junjie Wang, Dao Wen Tu, Ling Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title | Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title_full | Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title_fullStr | Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title_full_unstemmed | Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title_short | Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State |
title_sort | bradykinin inhibits oxidative stress-induced cardiomyocytes senescence via regulating redox state |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808370/ https://www.ncbi.nlm.nih.gov/pubmed/24204728 http://dx.doi.org/10.1371/journal.pone.0077034 |
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