Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.
Am J Physiol Cell Physiol. 2016 Mar 23;:ajpcell.00309.2015
Authors: Xu L, Wang L, Wen Z, Wu L, Jiang Y, Yang L, Xiao L, Xie Y, Ma M, Zhu W, Ye R, Liu X
Abstract
Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge pro-survival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24 h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 siRNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with caveolin-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, p-Raf and p-ERK were sequestered in Cav-1 siRNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway ...

Source: Am J Physiol Cell Ph... - March 22, 2016 Category: Cytology Authors: Xu L, Wang L, Wen Z, Wu L, Jiang Y, Yang L, Xiao L, Xie Y, Ma M, Zhu W, Ye R, Liu X Tags: Am J Physiol Cell Physiol Source Type: research