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Inhibition of phorbol ester-induced differentiation of HL-60 cells by long-chain (sphingoid) bases

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5202858
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HL-60 cells incubated with low concentrations of sphinganine failed to attach to petri dishes when treated for 24h with phorbol 12-myristate 13-acetate (PMA) of dioctanoylglycerol, which induce differentiation of these cells to adherent macrophages via activation of protein kinase C. PMA-dependent adherence was inhibited 50% by 3 ..mu..M sphinganine or 1 ..mu..M sphingosine. Sphinganine also blocked the inhibition of cell growth that occurs in response to PMA. These effects were not due to loss of cell viability, although higher concentrations were toxic. The effects were less apparent after 3 d, when considerable metabolism of (3-/sup 3/H)sphinganine had occurred. Other long-chain bases (e.g., stearylamine) were also inhibitory, but octylamine, N-acetylsphinganine and ceramides had no effect at similar concentrations. Sphinganine also decreased the binding of (/sup 3/H)phorbol dibutyrate by the phorbol receptor of HL-60 cells, protein kinase C. These results establish that long chain (sphingoid) bases inhibit protein kinase C in HL-60 cells and may function physiologically as negative effectors of this enzyme.

Research Organization:
Emory Univ. School of Medicine, Atlanta, GA
OSTI ID:
5202858
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADHESION
ANIMAL CELLS
BASES
BIOLOGICAL EFFECTS
CARCINOGENS
CELL DIFFERENTIATION
CONNECTIVE TISSUE CELLS
ENZYME ACTIVITY
ENZYMES
ESTERS
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MACROPHAGES
ORGANIC COMPOUNDS
PHAGOCYTES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
SOMATIC CELLS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS