Ceramide-induced apoptosis in fas-resistant Hodgkin's disease cell lines is caspase independent.
We investigated whether cell-permeable, synthetic ceramide (C6 ceramide) could induce apoptosis in Fas-resistant Hodgkin's disease (HD)-derived cell lines. Despite strongly expressing the Fas-receptor, two of three HD-derived cell lines were resistant to Fas-mediated apoptosis. This resistance to Fas could not be attributed to differential Fas isoform generation patterns between the Fas-resistant and the Fas-sensitive cell lines. The Fas-resistant cell lines did not demonstrate the presence of Fas exon 8 deletion. Bcl-2 and BclxL levels were comparable between the Fas-resistant and the Fas-sensitive cell lines. C6 ceramide could induce apoptosis in both Fas-resistant cell lines and this was associated with a decrease in BclxL level. Caspase-1, caspase-3, or pan-caspase inhibitors could not prevent ceramide-induced apoptosis. Furthur, ceramide treatment did not lead to cleavage of caspase 3 or poly(ADP-ribose) polymerase, but caused a loss in mitochondrial transmembrane potential which could not be prevented by caspase inhibitors. Thus, we conclude that ceramide-induced apoptosis in Fas-resistant HD cell lines is caspase independent.
Metkar
S S
SS
Immunology Division, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai, 400 012, India.
Anand
M
M
Manna
P P
PP
Naresh
K N
KN
Nadkarni
J J
JJ
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D019013:CD40 Antigens / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D015870:Gene Expression; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051020:bcl-X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; C494811:BCL2L1 protein, human; D019013:CD40 Antigens; D061945:Caspase Inhibitors; D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; C108637:aspartyl-glutamyl-valyl-aspartal; D051020:bcl-X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; C101954:N-caproylsphingosine; C096429:L 709049; D019319:Okadaic Acid; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D013755:Tetradecanoylphorbol Acetate