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 C-2-ceramide to CTLL-2 cells is found to block IL-2-induced cell cycle entry, as well as the apoptosis trigger ed by IL-2 deprivation, The protective effect of C-2-ceramide is achie ved only in the early stages following cytokine deprivation and is rel ated to the inhibition of bcl-x(L) degradation and the induction of a G(o) arrest of cells, The same treatment over a longer time when, as w e demonstrate, ceramide is produced physiologically, enhances cell dea th by apoptosis, The dual effect of ceramide both in protecting from o r inducing apoptosis is discussed further.