Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice

N. Noshita, T. Sugawara, M. Fujimura, Y. Morita-Fujimura, P. H. Chan

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

Release of cytochrome c from mitochondria to cytosol is a critical step in the mitochondrial-dependent signaling pathways of apoptosis. The authors have reported that manganese superoxide dismutase (Mn-SOD) attenuated cytochrome c release and apoptotic cell death after focal cerebral ischemia (FCI). To investigate downstream to the cytochrome c-dependent pathway, the authors examined caspase-9 activation after transient FCI by immunohistochemistry and Western blotting in both wild-type and Sod2 -/+ mice. Mice were subjected to 60 minutes of middle cerebral artery occlusion followed by 1, 2, 4, or 24 hours of reperfusion. Two hours after reperfusion, cytochrome c and caspase-9 were observed in the cytosol and significantly increased in Sod2 -/+ mutants compared with wild-type mice as shown by Western blotting. Immunofluorescent double labeling for cytochrome c and caspase-9 showed cytosolic cytochrome c 1 hour after transient FCI. Cleaved caspase-9 first appeared in the cytosolat2 hours and colocalized with cytochrome c. Terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick and labeling (TUNEL) showed significant increase of positive cells in Sod2 -/+ mice compared with the wild-type in the cortex, bur not in the caudate putamen. The current study revealed Mn-SOD might affect cytochrome c translocation and downstream caspase activation in the mitochondrial-dependent cell death pathway after transient FCI.

Original languageEnglish
Pages (from-to)557-567
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number5
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Caspase-9
  • Cerebral ischemia
  • Cytochrome c
  • Manganese superoxide dismutase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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