Peroxisome proliferator activated receptor (PPAR)-γ co-activator 1-α and hypoxia induced factor-1α mediate neuro- and vascular protection by hypoxic preconditioning in vitro

Preconditioning-induced cellular adaptation is a new therapeutic strategy for ischemic stroke. This research aims to examine the role of peroxisome proliferator activated receptor (PPAR)-gamma co-activator 1-alpha (PGC-1 alpha) and hypoxia induced factor-1 alpha (HIF-1 alpha) in hypoxic preconditioning-induced protection. In this study, rat artery endothelial cells and neuronal PC12 cells were preconditioned with hypoxia before oxygen-glucose deprivation (OGD) insult. Cell viability, protein expression and oxidative stress were then evaluated. PGC-1 alpha and HIF-1 alpha were knocked down by RNA interference. We found that hypoxic preconditioning significantly reduced cell damage, enhanced the expression of PGC-1 alpha, HIP-1 alpha and VEGF and attenuated oxidative stress in endothelial and PC12 cells in OGD model. The protective effects of hypoxic preconditioning were hardly detected in HIF-1 alpha or PGC-1 alpha deficit cells. The loss of protection was accompanied with a significant loss of VEGF expression in HIF-1 alpha or PGC-1 alpha deficit PC12 cells and PGC-1 alpha deficit endothelial cells as well as a considerable decrease of anti-oxidative effects in PGC-1 alpha knocked-down endothelial cells. The present study demonstrated that both PGC-1 alpha and HIF-1 alpha played crucial roles in hypoxic preconditioning in endothelial and neuronal cells. (C) 2012 Elsevier B.V. All rights reserved.