Dual role of ceramide in the control of apoptosis following IL-2 withdrawal.
Ceramide is largely known as a lipid second messenger with pleiotropic effects. Increases in ceramide levels have been related to the onset of apoptosis, terminal differentiation, or growth suppression. In this study, addition of exogenous C2-ceramide to CTLL-2 cells is found to block IL-2-induced cell cycle entry, as well as the apoptosis triggered by IL-2 deprivation. The protective effect of C2-ceramide is achieved only in the early stages following cytokine deprivation and is related to the inhibition of bcl-xL degradation and the induction of a G0 arrest of cells. The same treatment over a longer time when, as we demonstrate, ceramide is produced physiologically, enhances cell death by apoptosis. The dual effect of ceramide both in protecting from or inducing apoptosis is discussed further.
Flores
I
I
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain.
Martinez-A
C
C
Hannun
Y A
YA
Mérida
I
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002458:Cell Fractionation; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007376:Interleukin-2 / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic
D016895:Culture Media, Serum-Free; D004075:Diglycerides; D007376:Interleukin-2; C064769:N-acetylsphingosine; D011994:Recombinant Proteins; D013110:Sphingosine