Ischemia-induced release of cytochrome c from mitochondria and up-regulation of Bcl-2 expression in rat hippocampus.
- Author:
Chun-Yi ZHANG
1
;
Wan-Hua SHEN
;
Guang-Yi ZHANG
Author Information
1. Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221001, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Brain Ischemia;
metabolism;
Calcium Channel Blockers;
pharmacology;
Calcium Channels, L-Type;
drug effects;
Cytochromes c;
metabolism;
Cytosol;
Hippocampus;
metabolism;
Ketamine;
pharmacology;
Male;
Mitochondria;
metabolism;
Nifedipine;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
biosynthesis;
genetics;
Rats;
Rats, Sprague-Dawley;
Receptors, N-Methyl-D-Aspartate;
antagonists & inhibitors;
Up-Regulation
- From:
Acta Physiologica Sinica
2004;56(2):147-152
- CountryChina
- Language:English
-
Abstract:
To evaluate the effects of different antagonists on the release of cytochrome c from mitochondria to cytosol and the expression of Bcl-2 in mitochondria in rat hippocampus after ischemia, we examined Bcl-2 and cytochrome c expression by immunoblotting using 4-vessel occlusion (4-VO) as brain ischemia model. The results showed that after 24 h ischemia/reperfusion (I/R) cytochrome c decreased markedly in mitochondria, which was correspondingly increased in the cytosolic fraction. Bcl-2 expression was time-dependent, reaching its peak level after 6 h I/R. In all those samples, there were no alterations in the subcellular distribution of cytochrome oxidase, a mitochondrial respiratory chain protein. The decreases in Bcl-2 and cytochrome c in mitochondria were restored by pretreatment with non-competitive NMDA receptor antagonist ketamine or L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist nifedipine at 20 min prior to ischemia. The results demonstrate that the release of cytochrome c from mitochondria to cytosol and the up-regulation of Bcl-2 are possibly mediated by NMDA receptors or L-VGCC following brain ischemia. Cytochrome c release may be injurious while Bcl-2 up-regulation may be protective to ischemic hippocampus.
