Genistein induces apoptosis of RPE-J cells by opening mitochondrial PTP.
Although previous studies demonstrated that genistein-induced apoptosis of various cell types including RPE-J cells, the involvement of mitochondrial events in such types of apoptosis has not been demonstrated to date. In this investigation of genistein-induced apoptosis of RPE-J cells, genistein induced the reduction of the mitochondrial membrane potential and the release of cytochrome c to cytosol. A mitochondrial permeability transition pore (PTP) blocker bongkrekic acid prevented the reduction of the mitochondrial membrane potential and cytochrome c release, and consequently abolished caspase-3 activation, nuclear condensation, and DNA fragmentation. On the other hand, zVAD-fmk did not inhibit the mitochondrial event such as the reduction of the mitochondrial membrane potential and cytochrome c release although it prevented caspase-3 activation, nuclear condensation, and DNA fragmentation. Taken together, genistein induces apoptosis of RPE-J cells by opening the mitochondrial PTP, and the mitochondrial event in this type of apoptosis is caused independently of caspase.
Yoon
H S
HS
Department of Ophthalmology, Dong-A University College of Medicine, Pusan, South Korea. yhyoo@daunet.donga.ac.kr
Moon
S C
SC
Kim
N D
ND
Park
B S
BS
Jeong
M H
MH
Yoo
Y H
YH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D007473:Ion Channels; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore
D004791:Enzyme Inhibitors; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019833:Genistein