Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation.
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.
Okazaki
T
T
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Bell
R M
RM
Hannun
Y A
YA
D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D010169:Palmitic Acids; D013109:Sphingomyelins; D019308:Palmitic Acid; D013108:Sphingomyelin Phosphodiesterase; D002117:Calcitriol