title: Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia.
abstract: The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
authors.forename: Shang-Der
authors.initials: SD
authors.lastname: Chen
authors.forename: Ding-I
authors.initials: DI
authors.lastname: Yang
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Fu-Zen
authors.initials: FZ
authors.lastname: Shaw
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Yao-Chung
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D063269:Mitochondrial Turnover; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D000099156:Superoxide Dismutase 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000071246:Uncoupling Protein 2; D000099156:Superoxide Dismutase 2; C486497:PPARGC1A protein, human; C000604389:UCP2 protein, human
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