The effects of monobromobimane on calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome C release in isolated brain mitochondria.
A possible involvement of inhibitory effects of monobromobimane (MBM), a thiol reagent, on the swelling and the release of cytochrome c in the isolated brain mitochondria was examined. MBM dose-dependently inhibited the calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome c release. Significant relationships between mitochondrial swelling and cytochrome c release were detected. Furthermore, effects of in vivo treatment with MBM on neuronal cell damage after transient (15 min) global ischemia in rats were examined. Infusion of MBM (1 or 3 microg/animal) to cerebral ventricles attenuated an increased number of TUNEL-positive cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion. These results suggest that MBM may have an ability to inhibit mitochondria-associated apoptotic pathways through attenuation of the mitochondrial swelling and the release of cytochrome c.
Abe
Tsutomu
T
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Takagi
Norio
N
Nakano
Midori
M
Tanonaka
Kouichi
K
Takeo
Satoshi
S
D000818:Animals; D001152:Arsenicals / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects*; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D001152:Arsenicals; D001643:Bridged Bicyclo Compounds; D013439:Sulfhydryl Reagents; C029341:oxophenylarsine; D045304:Cytochromes c; D002118:Calcium; C028381:monobromobimane