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Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells
BACKGROUND: Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes s...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653516/ https://www.ncbi.nlm.nih.gov/pubmed/19272177 http://dx.doi.org/10.1186/1423-0127-16-12 |
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author | Hsieh, Chung-Yu Hsiao, Huai-Yu Wu, Wan-Yi Liu, Ching-Ann Tsai, Yu-Chih Chao, Yuen-Jen Wang, Danny L Hsieh, Hsyue-Jen |
author_facet | Hsieh, Chung-Yu Hsiao, Huai-Yu Wu, Wan-Yi Liu, Ching-Ann Tsai, Yu-Chih Chao, Yuen-Jen Wang, Danny L Hsieh, Hsyue-Jen |
author_sort | Hsieh, Chung-Yu |
collection | PubMed |
description | BACKGROUND: Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress. RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm(2)) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1. CONCLUSION: Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system. |
format | Text |
id | pubmed-2653516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26535162009-03-10 Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells Hsieh, Chung-Yu Hsiao, Huai-Yu Wu, Wan-Yi Liu, Ching-Ann Tsai, Yu-Chih Chao, Yuen-Jen Wang, Danny L Hsieh, Hsyue-Jen J Biomed Sci Research BACKGROUND: Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress. RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm(2)) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1. CONCLUSION: Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system. BioMed Central 2009-01-22 /pmc/articles/PMC2653516/ /pubmed/19272177 http://dx.doi.org/10.1186/1423-0127-16-12 Text en Copyright © 2009 Hsieh et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Hsieh, Chung-Yu Hsiao, Huai-Yu Wu, Wan-Yi Liu, Ching-Ann Tsai, Yu-Chih Chao, Yuen-Jen Wang, Danny L Hsieh, Hsyue-Jen Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title_full | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title_fullStr | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title_full_unstemmed | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title_short | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
title_sort | regulation of shear-induced nuclear translocation of the nrf2 transcription factor in endothelial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653516/ https://www.ncbi.nlm.nih.gov/pubmed/19272177 http://dx.doi.org/10.1186/1423-0127-16-12 |
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