Mitochondria permeability transition-dependent tert-butyl hydroperoxide-induced apoptosis in hepatoma HepG2 cells.
Tert-butyl hydroperoxide (t-BHP) has been demonstrated to induce apoptosis in hepatoma cell line HepG2, but poor data were available on the signaling pathway initiated by t-BHP. In this work, we studied in details the apoptotic pathways induced in HepG2 cells by t-BHP. DNA fragmentation, activation of caspases and cytochrome c release were demonstrated. Permeability transition pore inhibitors prevented the DNA fragmentation and caspase activation induced by t-BHP. In addition, changes in the mitochondrial membrane potential were detected: hyperpolarization preceded loss of membrane potential. It also preceded caspase activation which occurred before the induction of DNA fragmentation. Taken together, these results emphasize the central role played by mitochondria in the initiation of apoptosis in HepG2 cells exposed to oxidant agents.
Piret
Jean-Pascal
JP
Laboratory of Biochemistry and Cellular Biology, Facultés Universitaires Notre-Dame de la Paix, 61 rue de Bruxelles, 5000 Namur, Belgium. jppiret@fundp.ac.be
Arnould
Thierry
T
Fuks
Bruno
B
Chatelain
Pierre
P
Remacle
José
J
Michiels
Carine
C
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D045304:Cytochromes c; D020122:tert-Butylhydroperoxide; D020169:Caspases