Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival.
Mitochondria are the powerhouse of the cell. Their primary physiological function is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Reactive oxygen species generated from mitochondria have been implicated in acute brain injuries such as stroke and neurodegeneration. Recent studies have shown that mitochondrially-formed oxidants are mediators of molecular signaling, which is implicated in the mitochondria-dependent apoptotic pathway that involves pro- and antiapoptotic protein binding, the release of cytochrome c, and transcription-independent p53 signaling, leading to neuronal death. Oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves phosphatidylinositol 3-kinase/Akt and downstream signaling, which lead to neuronal survival. Genetically modified mice or rats that over-express or are deficient in superoxide dismutase have provided strong evidence in support of the role of mitochondrial dysfunction and oxidative stress as determinants of neuronal death/survival after stroke and neurodegeneration.
Niizuma
Kuniyasu
K
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305-5487, USA.
Endo
Hidenori
H
Chan
Pak H
PH
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D051028:bcl-2-Associated X Protein / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D011518:Proto-Oncogene Proteins; C000606290:SOD1 protein, human; D051028:bcl-2-Associated X Protein; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1