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Modulation of cell growth and differentiation by ceramide
Author(s) -
Bielawska Alicja,
Linardic Corinne M.,
Hannun Yusuf A.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80769-d
Subject(s) - ceramide , modulation (music) , microbiology and biotechnology , chemistry , cell growth , biochemistry , biology , apoptosis , physics , acoustics
Ceramide has been suggested as an intracellular modulator of cell growth and differentiation [Okazaki, T. el al. (1990) J. Biol. Chem. 265, 15823‐15831]. In this study, parameters that modulate the effects of ceramide on HL‐60 cell growth and differentiation were examined. A short‐chain, cell‐permeable analog of ceramide, C 2 ‐ceramide, induced differentiation of HL‐60 human leukemia cells and inhibited HL‐60 growth in a concentration‐dependent manner. The potency of C 2 ‐ceramide was modulated by the starting cell density such that the concentration of C 2 ‐ceramide producing 50% inhibition of cell growth (IC 50% ) ranged from 2 μM (for cells suspended at 1 × 10 5 cells/ml) to 11 μM (for cells at 8 × 10 5 cells/ml). However, the IC 50% showed little variation if the concentration of C 2 ‐ceramide was expressed as fmol of C 2 ‐ceramide per 10 5 cells. Therefore, the effectiveness of C 2 ‐ceramide appeared to be primarily determined by its cellular rather than molar concentration. Binding of C 2 ‐ceramide to serum proteins resulted in a 10‐fold increase in the IC 50% . These results demonstrate that the biologic activity of C 2 ‐ceramide is subject to surface dilution kinetics and is sensitive to the presence of lipid‐binding proteins. In these properties, ceramide behaves as a prototypic lipid second messenger/intracellular mediator.