Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis.
The 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 (delta psi(m)) showed that both H2O2 and TBT dissipated delta psi(m), but with different time courses. TBT caused a concomitant loss of delta psi(m) and release of cytochrome c, whereas cytochrome c release and caspase activation preceded any apparent delta psi(m) loss in H2O2-treated cells. Thus, our results suggest that different mechanisms are involved in triggering cytochrome c release with these apoptosis-inducing agents.
Stridh
H
H
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Kimland
M
M
Jones
D P
DP
Orrenius
S
S
Hampton
M B
MB
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D003574:Cytochrome c Group; D014220:Trialkyltin Compounds; C011559:tributyltin; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases