Selective involvement of caspase-3 in ceramide induced apoptosis in AK-5 tumor cells.
Ceramide, a product of sphingomyelin metabolism, is a novel lipid second messenger that mediates diverse cellular functions. The present study demonstrates the activation of caspase-3/CPP-32beta, during apoptosis induced by cell permeable exogenous ceramides, in AK-5 tumor, a spontaneously regressing rat histiocytoma. The apoptotic events were suppressed by the caspase-3 specific tetrapeptide inhibitor DEVD-CHO but not by the caspase-1 inhibitor YVAD-CMK. In cells overexpressing Bcl-2, a significant decrease in cell death was observed after exogenous addition of ceramides. Furthermore the processing of caspase-3 to its active form upon apoptotic stimulus, and the subsequent cleavage of the substrate PARP, suggested a central role for caspase-3 in the ceramide mediated apoptosis in AK-5 tumor cells.
Anjum
R
R
Centre for Cellular and Molecular Biology, Hyderabad, India.
Ali
A M
AM
Begum
Z
Z
Vanaja
J
J
Khar
A
A
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002518:Ceramides / Q000494:pharmacology*; D004789:Enzyme Activation; D010447:Peptide Hydrolases / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D002518:Ceramides; D011065:Poly(ADP-ribose) Polymerases; D010447:Peptide Hydrolases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases