Selective involvement of caspase-3 in ceramide induced apoptosis in AK-5 tumor cells.

Abstract

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.

• Authors: R Anjum, A M Ali, Z Begum, J Vanaja, A Khar
• Journal: FEBS letters (FEBS Lett) Vol. 439 Issue 1-2 Pg. 81-4 (Nov 13 1998) ISSN: 0014-5793 [Print] England
• PMID: 9849882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• Poly(ADP-ribose) Polymerases
• Peptide Hydrolases
• Casp3 protein, rat
• Caspase 3
• Caspases

Topics

• Animals
• Apoptosis
• Caspase 3
• Caspases (metabolism)
• Ceramides (pharmacology)
• Enzyme Activation
• Peptide Hydrolases (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Rats
• Rats, Wistar
• Tumor Cells, Cultured