Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury

A. Lewén, M. Fujimura, T. Sugawara, P. Matz, J. C. Copin, P. H. Chan

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)914-920
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number8
DOIs
Publication statusPublished - 2001

Keywords

  • Aconitase
  • Cell death
  • Head injury
  • Outcome
  • Reactive oxygen species
  • SOD2

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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