Ceramide Synergizes with Phorbol Ester or Okadaic Acid to Induce IκB Degradation

• Published in: Biochemical and biophysical research communications Vol. 263; no. 1; pp. 63 - 67
• Main Authors: Fernandez, Paula C., Dobbelaere, Dirk A.E.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.09.1999
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1312

Ceramide is a lipid second messenger which is generated in response to stimulation of a number of surface receptors, treatment with chemotherapeutic agents, or ionising radiation. Depending on the target cell, ceramide induces diverse biological responses including apoptosis, cell-cycle arrest, differentiation, and also proliferation. We studied the effect of ceramide on the degradation of IκB, the cytoplasmic inhibitor of the transcription factor NF-κB. We show that ceramide treatment results in reduced levels of phosphorylated IκBα and degradation of both IκBα and IκBβ. Ceramide synergised with okadaic acid (OA), a compound which interferes with the protein phosphatase 2A-controlled component of the NF-κB activation pathway, enhancing OA-induced IκB degradation. Ceramide also synergised with phorbol 12-myristate 13-acetate, which mimics protein kinase C activation. Finally, we show that the synergistic effect of ceramide with OA or phorbol ester can be observed in primary lymph node T-cells as well as in transformed T-cells.