Kitagawa S, Nojiri H, Nakamura M, Gallagher R E, Saito M
Division of Hemopoiesis, Jichi Medical School, Tochigi-ken, Japan.
J Biol Chem. 1989 Sep 25;264(27):16149-54.
We have recently reported that neolacto series gangliosides (NeuAc-nLc) are increased during granulocytic differentiation of human myelogenous leukemia cell line HL-60 cells induced by retinoic acid and that HL-60 cells are differentiated into mature granulocytes when the cells are cultivated with NeuAc-nLc (Nojiri, H., Kitagawa, S., Nakamura, M., Kirito, K., Enomoto, Y., and Saito, M. (1988) J. Biol. Chem. 263, 7443-7446). In contrast to these wild-type-HL-60 cells, HL-60 cells resistant to differentiation induction by retinoic acid showed a markedly decreased content of gangliosides, especially NeuAc-nLc, and did not show any increase in the content of gangliosides when cultivated with retinoic acid. Neutral glycosphingolipids, the precursors of gangliosides, were not accumulated in these resistant cells. When retinoic acid-resistant HL-60 cells were cultivated in the presence of NeuAc-nLc, the cells were found to be differentiated into mature granulocytes on morphological and functional criteria. The differentiation of cells was dependent on the concentration of gangliosides and was accompanied by inhibition of cell growth. Wild-type HL-60 cells differentiated by NeuAc-nLc showed the changes in ganglioside composition, which were similar to those in wild-type HL-60 cells differentiated by retinoic acid; among the gangliosides changed, 2----3 sialylparagloboside and 2----3 sialylnorhexaosylceramide were increased. These findings suggest (a) that the synthesis of particular NeuAc-nLe molecules is an important step for retinoic acid-induced granulocytic differentiation and this step could be bypassed or replaced by exogenous NeuAc-nLc, and (b) that the defective synthesis of particular NeuAc-nLc molecules is responsible for the failure of differentiation induction in retinoic acid-resistant HL-60 cells by retinoic acid.
我们最近报道，在维甲酸诱导人髓性白血病细胞系HL-60细胞进行粒细胞分化的过程中，新乳糖系列神经节苷脂（NeuAc-nLc）含量增加，并且当HL-60细胞与NeuAc-nLc一起培养时，HL-60细胞可分化为成熟粒细胞（野尻，H.，北川，S.，中村，M.，桐仁，K.，榎本，Y.，以及斋藤，M.（1988年）《生物化学杂志》263卷，7443 - 7446页）。与这些野生型HL-60细胞相反，对维甲酸诱导分化有抗性的HL-60细胞神经节苷脂含量明显降低，尤其是NeuAc-nLc，并且在用维甲酸培养时神经节苷脂含量未出现任何增加。神经节苷脂的前体中性糖鞘脂在这些抗性细胞中并未积累。当抗维甲酸的HL-60细胞在NeuAc-nLc存在的情况下培养时，根据形态学和功能标准发现这些细胞可分化为成熟粒细胞。细胞的分化取决于神经节苷脂的浓度，并且伴随着细胞生长的抑制。由NeuAc-nLc诱导分化的野生型HL-60细胞显示出神经节苷脂组成的变化，这与由维甲酸诱导分化的野生型HL-60细胞中的变化相似；在发生变化的神经节苷脂中，2----3唾液酸副球蛋白和2----3唾液酸神经六糖神经酰胺增加。这些发现表明：（a）特定NeuAc-nLe分子的合成是维甲酸诱导粒细胞分化的重要步骤，并且这一步骤可以被外源性NeuAc-nLc绕过或替代；（b）特定NeuAc-nLc分子的合成缺陷是抗维甲酸的HL-60细胞中维甲酸诱导分化失败的原因。
