Ischemia-induced release of cytochrome c from mitochondria and up-regulation of Bcl-2 expression in rat hippocampus.
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.
Zhang
Chun-Yi
CY
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221001, China.
Shen
Wan-Hua
WH
Zhang
Guang-Yi
GY
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D003600:Cytosol; D006624:Hippocampus / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D045304:Cytochromes c; D009543:Nifedipine