title: Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury.
abstract: Mitochondrial cytochrome c translocation to the cytosol initiates the mitochondrial-dependent apoptotic pathway. This event has not been previously reported in traumatic brain injury (TBI). The authors determined the expression of cytochrome c in cytosolic and mitochondrial fractions after severe TBI produced by the controlled cortical impact model in the mouse. One hour after trauma there was an increase in cytosolic cytochrome c immunoreactivity. The increases in cytosolic cytochrome c preceded DNA fragmentation, which started at 4 hours. Western blots of mitochondrial and cytosolic fractions confirmed that there was a translocation of cytochrome c from the mitochondria after TBI. Mice deficient in manganese superoxide dismutase (MnSOD) showed an increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death 4 and 24 hours after injury compared with wild-type control mice. However, the overall cell death was increased in MnSOD mice, as illustrated by a larger cortical lesion in these animals. The results show that cytochrome c is released from the mitochondria after severe TBI partly by a free radical-dependent mechanism, and that massive mitochondrial cytochrome c release is a predictor of necrotic cell death rather than apoptosis.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305-5487, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lewén
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: P
authors.initials: P
authors.lastname: Matz
authors.forename: J C
authors.initials: JC
authors.lastname: Copin
authors.forename: P H
authors.initials: PH
authors.lastname: Chan
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D003574:Cytochrome c Group / Q000378:metabolism*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D003574:Cytochrome c Group