Y. Zhan et al., The roles of caspase-3 and bcl-2 in chemically-induced apoptosis but not necrosis of renal epithelial cells, ONCOGENE, 18(47), 1999, pp. 6505-6512
The kidney is a target for toxicants including cisplatin and S-(1,2-dichlor
ovinyl)-L-cysteine (DCVC), a metabolite of the environmental contaminant, t
richloroethylene. Necrosis is well characterized in kidney cells, but pathw
ays leading to apoptosis are less clear. Cysteine conjugates are useful tox
icants because they induce either necrosis or apoptosis depending on chemic
al structure or antioxidant status. Herein, we show that in the renal epith
elial cell line LLC-PK1, activation of caspase3 (CPP32/Yama/apopain) is cru
cial for apoptosis, but not necrosis. Apoptosis was blocked by zVAD.fmk, an
d partially by a cathepsin inhibitor. Caspase-3 activity and cleavage of po
ly(ADP-ribose) polymerase (PARP) was detected only during apoptosis. S-(1,1
,2,2-Tetrafluoroethyl)-1-cysteine (TFEC), a metabolite of tetrafluoroethyle
ne, kills cells only by necrosis, and did not activate caspases under any c
onditions. Apoptosis and activation of caspase3 by cisplatin, but not DCVC,
was prevented by bcl-2. Thus, caspase-3 activation by bcl-2-dependent and
-independent mechanisms is a terminal event in chemical-apoptosis of renal
epithelial cells.