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

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• 作者：Jia Zhao^a ; ^{apolloathene@126.com} ; Ling Li^b ; ^{gzlilings@yahoo.com.cn} ; Zhong Pei^b ; ^{peizhong@mail.sysu.edu.cn} ; Chaoying Li^b ; ^{cly11157@126.com} ; Huan Wei^c ; ^{weihuan2010@yahoo.cn} ; Bo Zhang^d ; ^{bozhang.1982@yahoo.com.cn} ; Ying Peng^a ; ^{docpengy@yahoo.com.cn} ; Ying Wang^b ; ^{wy8401@sina.com} ; Yuqian Tao^b ; ^{yuqiantao@yahoo.com.cn} ; Ruxun Huang^b ; ^{hrx998@yahoo.com.cn}
• 关键词：PGC-1伪 ; Peroxisome Proliferator Activated Receptor (PPAR)-纬 Co-activator 1-伪 ; HIF-1伪 ; Hypoxia induced factor-1伪 ; VEGF ; vascular endothelial growth factor ; ROS ; reactive oxygen species ; PC12 ; rat pheochromocytoma ; OGD ; Oxygen&ndash ; glucose deprivation
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：4 April, 2012
• 卷：1447
• 期：Complete
• 页码：1-8
• 文件大小：852 K

摘要

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)-纬 co-activator 1-伪 (PGC-1伪) and hypoxia induced factor-1伪 (HIF-1伪) 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伪 and HIF-1伪 were knocked down by RNA interference. We found that hypoxic preconditioning significantly reduced cell damage, enhanced the expression of PGC-1伪, HIF-1伪 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伪 or PGC-1伪 deficit cells. The loss of protection was accompanied with a significant loss of VEGF expression in HIF-1伪 or PGC-1伪 deficit PC12 cells and PGC-1伪 deficit endothelial cells as well as a considerable decrease of anti-oxidative effects in PGC-1伪 knocked-down endothelial cells. The present study demonstrated that both PGC-1伪 and HIF-1伪 played crucial roles in hypoxic preconditioning in endothelial and neuronal cells.