Inhibition of phorbol ester-induced differentiation of HL-60 cells by long-chain (sphingoid) bases
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-; TRN: 86-031631
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
CELL DIFFERENTIATION
BASES
BIOLOGICAL EFFECTS
PHORBOL ESTERS
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
ADHESION
INHIBITION
MACROPHAGES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
CARCINOGENS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
ORGANIC COMPOUNDS
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
SOMATIC CELLS
TRANSFERASES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques