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

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-...

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Bibliographic Details
Published in:Journal of biomedical science 2009-01, Vol.16 (1), p.12-12
Main Authors: Hsieh, Chung-Yu, Hsiao, Huai-Yu, Wu, Wan-Yi, Liu, Ching-Ann, Tsai, Yu-Chih, Chao, Yuen-Jen, Wang, Danny L, Hsieh, Hsyue-Jen
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - physiology
Cell Nucleus - metabolism
Cells, Cultured
Endothelial Cells - cytology
Endothelial Cells - metabolism
Enzyme Inhibitors - metabolism
Gene Expression Regulation
Heme Oxygenase-1 - genetics
Heme Oxygenase-1 - metabolism
Humans
Hydrogen Peroxide - metabolism
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - metabolism
Oxidants - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Reactive Oxygen Species - metabolism
Shear Strength
Stress, Mechanical
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Summary: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. 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. 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.
ISSN:1423-0127
1021-7770
1423-0127
DOI:10.1186/1423-0127-16-12