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Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim

Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels....

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Autores principales: Li, Yao, Ren, Meng, Wang, Xiaoqun, Cui, Xingxing, Zhao, Hongmei, Zhao, Chuanrong, Zhou, Jing, Guo, Yanan, Hu, Yi, Yan, Chen, Berk, Bradford, Wang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686153/
https://www.ncbi.nlm.nih.gov/pubmed/29138498
http://dx.doi.org/10.1038/s41598-017-15672-3
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author Li, Yao
Ren, Meng
Wang, Xiaoqun
Cui, Xingxing
Zhao, Hongmei
Zhao, Chuanrong
Zhou, Jing
Guo, Yanan
Hu, Yi
Yan, Chen
Berk, Bradford
Wang, Jing
author_facet Li, Yao
Ren, Meng
Wang, Xiaoqun
Cui, Xingxing
Zhao, Hongmei
Zhao, Chuanrong
Zhou, Jing
Guo, Yanan
Hu, Yi
Yan, Chen
Berk, Bradford
Wang, Jing
author_sort Li, Yao
collection PubMed
description Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels. However, the molecular mechanism responsible for flow-induced beneficial effects is incompletely understood. Here we report the role of glutaredoxin 1 (Grx1), an antioxidant enzyme, in flow-mediated protective effect in endothelial cells. Specifically, we found that Grx1 is markedly up-regulated by the steady laminar flow. Increasing Grx1 reduces the pro-apoptotic protein Bim expression through regulating Akt-FoxO1 signaling and also attenuates H(2)O(2)-induced Bim activation via inhibiting JNK phosphorylation, subsequently preventing the apoptosis of endothelial cells. Grx1 knockdown abolishes the inhibitory effect of steady laminar flow on Bim. The inhibitory effect of Grx1 on Bim is dependent on Grx1′s thioltransferase activity. These findings indicate that Grx1 induction plays a key role in mediating the protective effect of laminar blood flow and suggest that Grx1 may be a potential therapeutic target for atherosclerosis.
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spelling pubmed-56861532017-11-21 Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim Li, Yao Ren, Meng Wang, Xiaoqun Cui, Xingxing Zhao, Hongmei Zhao, Chuanrong Zhou, Jing Guo, Yanan Hu, Yi Yan, Chen Berk, Bradford Wang, Jing Sci Rep Article Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels. However, the molecular mechanism responsible for flow-induced beneficial effects is incompletely understood. Here we report the role of glutaredoxin 1 (Grx1), an antioxidant enzyme, in flow-mediated protective effect in endothelial cells. Specifically, we found that Grx1 is markedly up-regulated by the steady laminar flow. Increasing Grx1 reduces the pro-apoptotic protein Bim expression through regulating Akt-FoxO1 signaling and also attenuates H(2)O(2)-induced Bim activation via inhibiting JNK phosphorylation, subsequently preventing the apoptosis of endothelial cells. Grx1 knockdown abolishes the inhibitory effect of steady laminar flow on Bim. The inhibitory effect of Grx1 on Bim is dependent on Grx1′s thioltransferase activity. These findings indicate that Grx1 induction plays a key role in mediating the protective effect of laminar blood flow and suggest that Grx1 may be a potential therapeutic target for atherosclerosis. Nature Publishing Group UK 2017-11-14 /pmc/articles/PMC5686153/ /pubmed/29138498 http://dx.doi.org/10.1038/s41598-017-15672-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Yao
Ren, Meng
Wang, Xiaoqun
Cui, Xingxing
Zhao, Hongmei
Zhao, Chuanrong
Zhou, Jing
Guo, Yanan
Hu, Yi
Yan, Chen
Berk, Bradford
Wang, Jing
Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title_full Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title_fullStr Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title_full_unstemmed Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title_short Glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting Bim
title_sort glutaredoxin 1 mediates the protective effect of steady laminar flow on endothelial cells against oxidative stress-induced apoptosis via inhibiting bim
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686153/
https://www.ncbi.nlm.nih.gov/pubmed/29138498
http://dx.doi.org/10.1038/s41598-017-15672-3
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