各种分化诱导剂对人白血病HL-60细胞内中性糖脂合成的影响

作者采用[~(14)C]-标记的半乳糖研究HL-60细胞分化过程中中性糖脂的合成,以了解佛波酯(TPA)、二甲基亚砜(DMSO]、GM3(NeuAc-Gal-Glc-Cer)、GMI[Gal-GalNAc-(NeuAc)Gal-Glc-Cer]和硫脂对其生物合成的影响。TPA、GM3不但能诱导HL-60细胞分化为单核细胞,而且明显地增加[~(14)C]-半乳糖的掺入。TPAGM3在不同程度上促进[~(14)C]-标记的中性糖脂合成,其中主要促进二己糖基神经酰胺(GL2)合成。DMSO诱导HL-60细胞分化为粒细胞,不仅显著地抑制了[~(14)C]-半乳糖掺入,而且抑制了[~(14)C]-标记的中性糖脂的合成,但是促进-已糖基神经酰胺[GL1]的合成。这些结果提示中性糖脂的生物合成与HL-60细胞的分化有关。

EFFECTS OF DIFFERENTIATING INDUCERS ON THE BIOSYNTHESIS OF NEUTRAL GLYCOLIPIDS BY HL-60 PROMYELOCYTIC LEUKEMIA CELLS

The relationship between glycosphingolipid synthesis and cellular growth and differentiation was investigated by measuring the incorporation of [14C]-galactose into the glycolipids of HL-60 promyelocytic leukemia cells exposed to either 12-o-tetradecanoylphorbol 13-acetate (TPA), dimethylsulfoxide (DMSO), GM3, GM1, or sulfatides. All of these agents, except sulfatides, inhibited the growth of HL-60 calls and TPA, DMSO, and GM3 induced their differentiation. Incorporation of [14C]-galactose into trichloroacetic acidpreoipitable material was increased in cells treated with TPA, GM3, or GM1, and decreased in cells exposed to DMSO or sulfatides. The incorporation of [14C]-galaotose into neutral glycosphingolipids was increased in cells with TPA, GM3, and GM1 and decreased in cells grown in the presence of DMSO or sulfatides. In cells treated with TPA, GM3, or GM1, the synthesis of GL2, a precursor of GM3, was significantly greater than in control cells. This presumably accounts for the increased synthesis of GM3 in cells treated with the inducers of cellular differentiation. In addition, HL-60 cells grown either in the absence or the presence of TPA, DMSO, GM3, GM1, and sulfatide were found to synthesize glucosylceramide and small amounts of galaotosyloera-mide. Galactosyloeramide synthesis was greater in cells treated with TPA than in gells treated with other agents. The findings indicate that glycosphingolipid metabolism is significantly modified in HL-60 leukemia cells under differentiation induction.