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

• Published in: Brain research 2001-03, Vol.896 (1), p.69-76
• Main Authors: Li, Ping-An, He, Qing-Ping, Ouyang, Yi-Bing, Liu, Chun-Li, Hu, Bing-Ren, Siesjö, Bo K.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Caspase 3; Caspases - metabolism; Cell Death - physiology; Cerebral ischemia; Cytochrome c; Cytochrome c Group - analysis; Cytochrome c Group - metabolism; Hyperglycemia; Hyperglycemia - metabolism; In Situ Nick-End Labeling; Ischemic Attack, Transient - metabolism; Male; Medical sciences; Mitochondria; Mitochondria - enzymology; Neurology; Neuronal death; Neurons - cytology; Neurons - enzymology; Prosencephalon - blood supply; Prosencephalon - cytology; Prosencephalon - metabolism; Rats; Rats, Wistar; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)01997-7

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.