Bidirectional Regulation of Concentration-dependent Effect of Zn~(2+) on PTP Opening and Cytochrome c Release

Mitochondria are endowed with multiple Ca 2+ transport mechanisms by which they take up cytosolic Ca 2+ and in turn induces opening of permeability transition pores(PTP) and disrupts the mitochondria membrane potential(ΔΨm).The collapse of ΔΨm along with the release of cytochrome c from mitochondria is followed by activation caspases and apoptosis.However,the mechanism for the regulation of this system is poorly understood.The effect of Zn 2+ were examined on PTP opening and cytochrome c release mediated by Ca 2+ in mitochondria from rat hepacytein vitro. Results from UV spectrophotometer and Western blot revealed that the effect of Zn 2+ was biphasic:high dose was more 150 μmol/L Zn 2+ inhibit completely PTP opening mediated by Ca 2+ and cytochrome c release. As the doses decreased to 50～100 μmol/L Zn 2+ , the inhibition action was declined,whereas low dose of 0.2～0.5 μmol/L Zn 2+ accelerated the PTP opening and cytochrome c release. Both high and low doses of Zn 2+ could completely or partially destroy mitochondrial membrane potential measured by fluorescence spectrophotometry.The dual_directional regulation observed for PTP opening and cytochrome c release by Zn 2+ was concentration dependent,and might be involved in the collapse of mitochondrial membrane potential and Ca 2+ _induced Ca 2+ release from mitochondria.