Early release of cytochrome C and activation of caspase-3 in hyperglycemic rats subjected to transient forebrain ischemia

Brain Res. 2001 Mar 30;896(1-2):69-76. doi: 10.1016/s0006-8993(01)01997-7.

Abstract

The mechanisms underlying the aggravating effect of hyperglycemia on brain damage are still elusive. The present study was designed to test our hypothesis that hyperglycemia-mediated damage is caused by mitochondrial dysfunction with mitochondrial release of cytochrome c (cyt c) to the cytoplasm, which leads to activation of caspase-3, the executioner of cell death. We induced 15 min of forebrain ischemia, followed by 0.5, 1, and 3 h of recirculation in sham, normoglycemic and hyperglycemic rats. Release of cyt c was observed in the neocortex and CA3 in hyperglycemic rats after only 0.5 h of reperfusion, when no obvious neuronal damage was observed. The release of cyt c persisted after 1 and 3 h of reperfusion. Activation of caspase-3 was observed after 1 and 3 h of recovery in hyperglycemic animals. No cyt c release or caspase-3 activation was observed in sham-operated controls while a mild increase of cyt c was observed in normoglycemic ischemic animals after 1 and 3 h of reperfusion. The findings that there is caspase activation and cyt c relocation support a notion that the biochemical changes that constitute programmed cell death occur after ischemia and contribute, at least in part, to hyperglycemia-aggravated ischemic neuronal death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism*
  • Cell Death / physiology
  • Cytochrome c Group / analysis
  • Cytochrome c Group / metabolism*
  • Hyperglycemia / metabolism*
  • In Situ Nick-End Labeling
  • Ischemic Attack, Transient / metabolism*
  • Male
  • Mitochondria / enzymology
  • Neurons / cytology
  • Neurons / enzymology
  • Prosencephalon / blood supply
  • Prosencephalon / cytology
  • Prosencephalon / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Cytochrome c Group
  • Casp3 protein, rat
  • Caspase 3
  • Caspases