Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis

AbstractThe ability of H2O2 and tributyltin (TBT) to trigger pro-caspase activation via export of cytochrome c from mitochondria to the cytoplasm was investigated. Treatment of Jurkat T lymphocytes with H2O2 resulted in the appearance of cytochrome c in the cytosol within 2 h. This was at least 1 h before caspase activation was observed. TBT caused cytochrome c release already after 5 min, followed by caspase activation within 1 h. Measurement of mitochondrial membrane potential (ΔΨm) showed that both H2O2 and TBT dissipated ΔΨm, but with different time courses. TBT caused a concomitant loss of ΔΨm and release of cytochrome c, whereas cytochrome c release and caspase activation preceded any apparent ΔΨm loss in H2O2-treated cells. Thus, our results suggest that different mechanisms are involved in triggering cytochrome c release with these apoptosis-inducing agents