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J. Biol. Chem., Vol. 264, Issue 32, 19076-19080, 11, 1989
T Okazaki, RM Bell and YA Hannun
Sphingolipid metabolism was examined in human promyelocytic leukemia HL- 60
cells. Differentiation of HL-60 cells with 1 alpha, 25- dihydroxyvitamin D3
(vitamin D3; 100 nM) was accompanied by sphingomyelin turnover. Maximum
turnover of [3H]choline-labeled sphingomyelin occurred 2 h following
vitamin D3 treatment, with sphingomyelin levels decreasing to 77 +/- 6% of
control and returning to base-line levels by 4 h. Ceramide and
phosphorylcholine were concomitantly generated. Ceramide mass levels
increased by 55% at 2 h following vitamin D3 treatment and returned to
base-line levels by 4 h. The amount of phosphorylcholine produced equaled
the amount of sphingomyelin hydrolyzed, suggesting the involvement of a
sphingomyelinase. Vitamin D3 treatment resulted in a 90% increase in the
activity of a neutral sphingomyelinase from HL-60 cells. The inferred role
of sphingomyelin hydrolysis in the induction of cell differentiation was
investigated using an exogenous sphingomyelinase. When a bacterial
sphingomyelinase was added at concentrations that caused a similar degree
of sphingomyelin hydrolysis as 100 nM vitamin D3, it enhanced the ability
of subthreshold levels of vitamin D3 to induce HL-60 cell differentiation.
This study demonstrates the existence of a "sphingomyelin cycle" in human
cells. Such sphingolipid cycles (Hannun, Y., and Bell, R. (1989) Science
243, 500-507) may function in a signal transduction pathway and in cellular
differentiation.
Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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