Ceramide synergizes with phorbol ester or okadaic acid to induce I kappa Bdegradation

Ceramide is a lipid second messenger which is generated in response to stim ulation of a number of surface receptors, treatment with chemotherapeutic a gents, or ionising radiation. Depending on the target cell, ceramide induce s diverse biological responses including apoptosis, cell-cycle arrest, diff erentiation, and also proliferation. We studied the effect of ceramide on t he degradation of I kappa B, the cytoplasmic inhibitor of the transcription factor NF-kappa B. We show that ceramide treatment results in reduced leve ls of phosphorylated I kappa B alpha and degradation of both I kappa B alph a and I kappa B beta. Ceramide synergised with okadaic acid (OA), a compoun d which interferes with the protein phosphatase 2A-controlled component of the NF-kappa B activation pathway, enhancing OA-induced I kappa B degradati on. Ceramide also synergised with phorbol 12-myristate 13-acetate, which mi mics protein kinase C activation. Finally, we show that the synergistic eff ect of ceramide with OA or phorbol ester can be observed in primary lymph n ode T-cells as well as in transformed T-cells. (C) 1999 Academic Press.