title: Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia.
abstract: Mitochondrial dysfunction may underlie both acute and delayed neuronal cell death resulting from cerebral ischemia. Specifically, postischemic release of mitochondrial constituents such as the pro-apoptotic respiratory chain component cytochrome c could contribute acutely to further mitochondrial dysfunction and to promote delayed neuronal death. Experiments reported here tested the hypothesis that ischemia or severe hypoxia results in release of cytochrome c from mitochondria. Cytochrome c was measured spectrophotometrically from either the cytosolic fraction of cortical brain homogenates after global ischemia plus reperfusion, or from brain slices subjected to severe hypoxia plus reoxygenation. Cytochrome c content in cytosol derived from cerebral cortex was increased after ischemia and reperfusion. In intact hippocampal slices, there was a loss of reducible cytochrome c after hypoxia/ reoxygenation, which is consistent with a decrease of this redox carrier in the mitochondrial pool. These results suggest that cytochrome c is lost to the cytosol after cerebral ischemia in a manner that may contribute to postischemic mitochondrial dysfunction and to delayed neuronal death.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pérez-Pinzón
authors.forename: G P
authors.initials: GP
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Born
authors.forename: J
authors.initials: J
authors.lastname: Lorenzo
authors.forename: R
authors.initials: R
authors.lastname: Busto
authors.forename: M
authors.initials: M
authors.lastname: Rosenthal
authors.forename: T J
authors.initials: TJ
authors.lastname: Sick
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism / Q000473:pathology; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003574:Cytochrome c Group