Activation of caspase-3-like protease by digitonin-treated lysosomes.
Apoptosis, a naturally occurring programmed cell death or cell 'suicide', has been paid much attention as one of the critical mechanisms for morphogenesis and tissue remodeling. Activation of cysteine aspartases (caspases) is one of the critical steps leading to apoptosis. Although a mitochondria-mediated pathway has been postulated to be one of the activation mechanism of caspase-3, another subcellular compartment might be involved in the activation of the enzyme. The present study shows that the supernatant fraction of digitonin-treated lysosomes strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease. Activation of caspase-3-like protease by digitonin-treated lysosomal fractions was specifically suppressed by leupeptin and E-64, inhibitors of cysteine protease. These results indicate that leakage of lysosomal cysteine protease(s) into the cytosolic compartment might be involved in the activation of caspase-3-like protease.
Institute of Medical Science, Kurashiki Medical Center, Japan.
R
R
Ishisaka
T
T
Utsumi
M
M
Yabuki
T
T
Kanno
T
T
Furuno
M
M
Inoue
K
K
Utsumi
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D007202:Indicators and Reagents / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007202:Indicators and Reagents; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D004072:Digitonin