Laminar flow activation of ERK5 leads to cytoprotective eff ect via CHIP-mediated p53 ubiquitination in endothelial cells

Title
Laminar flow activation of ERK5 leads to cytoprotective eff ect via CHIP-mediated p53 ubiquitination in endothelial cells
Author(s)
임재향[임재향]우창훈
Keywords
Laminar fl ow; Endothelial apoptosis; ERK5; CHIP; p53
Issue Date
201112
Publisher
대한해부학회
Citation
Anatomy and Cell Biology, v.44, no.4, pp.265 - 273
Abstract
Atherosclerosis is readily observed in areas where disturbed flow is formed, while the atheroprotective region is found in areas with steady laminar fl ow (L-fl ow). It has been established that L-fl ow protects endothelial cells against endothelial dysfunction, including apoptosis and infl ammation. It has also been reported that extracellular signal-regulated kinase 5 (ERK5)regulated endothelial integrity and protected endothelial cells from vascular dysfunction and disease under L-fl ow. However, the molecular mechanism by which L-fl ow-induced ERK5 activation inhibits endothelial apoptosis has not yet been determined. Transcription factor p53 is a major pro-apoptotic factor which contributes to apoptosis in various cell types. In this study, we found that 15-deoxy-Δ(12,14)-prostaglandin J2 induced p53 expression and that endothelial apoptosis was reduced under the L-fl ow condition. Th is anti-apoptotic response was reversed by the biochemical inhibition of ERK5 activation. It was also found that activation of ERK5 protected endothelial apoptosis in a C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligasedependent manner. Moreover, molecular interaction between ERK5-CHIP and p53 ubiquitination were addressed with a CHIP ubiquitin ligase activity assay. Taken together, our data suggest that the ERK5-CHIP signal module elicited by L-fl ow plays an important role in the anti-apoptotic mechanism in endothelial cells.
URI
http://hdl.handle.net/YU.REPOSITORY/24002
ISSN
2093-3665
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의과대학 > 약리학교실 > Articles
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