Transforming growth factor beta 1 potently activates CPP32-like proteases in human hepatoma cells.
Induction of apoptosis in Hep3B hepatoma cells by transforming growth factor beta 1 (TGF-beta 1) was accompanied by the activation of interleukin-1-beta-converting-enzyme-like proteases, which have recently been renamed as caspases. The caspase inhibitor ZVAD-FMK, which has a broader specificity for caspase family proteases, blocked TGF-beta 1-induced apoptosis in a concentration-dependent manner. The caspases in this apoptotic process were further characterized by using a more specific caspase inhibitor, DEVD-FMK, for CPP32-like (caspase-3-like) proteases. Our results demonstrated that CPP32-like proteases were activated during apoptosis triggered by TGF-beta 1. Enhancement of CPP32-like activity was clearly detected in TGF-beta 1-treated Hep3B cells. Furthermore, cleavage of poly(ADP-ribose) polymerase, an in vivo substrate for CPP32, in these cells was confirmed by immunoblotting. Thus, we suggest that CPP32-like proteases participate in apoptotic cell death induced by TGF-beta 1.
Hung
W C
WC
School of Technology for Medical Sciences, Kaohsiung Medical College, Taiwan, Republic of China.
Chang
H C
HC
Chuang
L Y
LY
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D016212:Transforming Growth Factor beta; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases