cytochrome-c-t and oxophenylarsine

Mitochondria play a key role in the regulation of cell death, necrosis, and apoptosis. It is well known that the opening of the mitochondrial permeability transition pore (PTP) induces the cytochrome C release and results in apoptosis. Also, it has been reported that the inhibition of PTP by cyclosporin A prevents the ischemia/reperfusion-induced necrosis. Thus, the opening of mitochondrial PTP may be a central coordinating event of apoptotic and necrotic cell death. However, the relationship between PTP opening and both modes of cell death remains elusive. In this paper, we report the recent state of our research method and the role of mitochondrial PTP in cardiac cell death.

Topics: Apoptosis; Arsenicals; Calcium; Cyclosporine; Cytochromes c; Diazoxide; Humans; Ion Channels; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Reperfusion Injury; Myocardium; Necrosis; Ouabain

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.

Topics: Animals; Arsenicals; Blotting, Western; Bridged Bicyclo Compounds; Calcium; Cytochromes c; Dose-Response Relationship, Drug; Hippocampus; In Situ Nick-End Labeling; In Vitro Techniques; Ischemic Attack, Transient; Male; Mitochondria; Mitochondrial Swelling; Models, Biological; Rats; Rats, Wistar; Sulfhydryl Reagents