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 thi s investigation of genistein-induced apoptosis of RPE-J cells, genistein in duced 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 m embrane potential and cytochrome c release, and consequently abolished casp ase-3 activation, nuclear condensation, and DNA fragmentation, On the other hand, zVAD-fmk did not inhibit the mitochondrial event such as the reducti on of the mitochondrial membrane potential and cytochrome c release althoug h it prevented caspase-3 activation, nuclear condensation, and DNA fragment ation, Taken together, genistein induces apoptosis of RPE-J cells by openin g the mitochondrial PTP, and the mitochondrial event in this type of apopto sis is caused independently of caspase, (C) 2000 Academic Press.