title: 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.
abstract: 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)-γ co-activator 1-α (PGC-1α) and hypoxia induced factor-1α (HIF-1α) 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-1α and HIF-1α were knocked down by RNA interference. We found that hypoxic preconditioning significantly reduced cell damage, enhanced the expression of PGC-1α, HIF-1α 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-1α or PGC-1α deficit cells. The loss of protection was accompanied with a significant loss of VEGF expression in HIF-1α or PGC-1α deficit PC12 cells and PGC-1α deficit endothelial cells as well as a considerable decrease of anti-oxidative effects in PGC-1α knocked-down endothelial cells. The present study demonstrated that both PGC-1α and HIF-1α played crucial roles in hypoxic preconditioning in endothelial and neuronal cells.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, PR China. apolloathene@126.com
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.forename: Chaoying
authors.initials: C
authors.lastname: Li
authors.forename: Huan
authors.initials: H
authors.lastname: Wei
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Tao
authors.forename: Ruxun
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism; D016716:PC12 Cells; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors