Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells

Chung-Yu Hsieh, Huai-Yu Hsiao, Wan-Yi Wu, Ching-Ann Liu, Yu-Chih Tsai, Yuen-Jen Chao, Danny-Ling Wang, Hsyue-Jen Hsieh

研究成果: 雜誌貢獻文章

44 引文 斯高帕斯(Scopus)

摘要

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/cm2) 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.
原文英語
期刊Journal of Biomedical Science
16
發行號1
DOIs
出版狀態已發佈 - 2009
對外發佈Yes

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    Hsieh, C-Y., Hsiao, H-Y., Wu, W-Y., Liu, C-A., Tsai, Y-C., Chao, Y-J., Wang, D-L., & Hsieh, H-J. (2009). Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells. Journal of Biomedical Science, 16(1). https://doi.org/10.1186/1423-0127-16-12