Glycosaminoglycan metabolism of HL-60 cells during differentiation induction by tetradecanoylphorbol-13-acetate.
Many biochemical responses to phorbol ester differentiation inducers have been reported, including alterations in synthesis of specific gene products such as glycoproteins. Stage-specific glycosaminoglycan changes have previously been associated with the differentiation process, including a dramatic reduction in cellular chondroitin 4-sulfate during human myeloid leukemia cell maturation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). We have demonstrated that treatment of HL-60 human promyelocytic leukemia cells with 4-methyl-umbelliferyl-beta-D-xyloside increases precursor incorporation into glycosaminoglycans linked to beta-D-xyloside, rather than core protein, eliminating the need for core protein and xylosyltransferase. Therefore, these beta-D-xyloside-treated cells were used to study the decreased glycosaminoglycan production during TPA-induced HL-60 differentiation. Exposure of these pretreated HL-60 cells to TPA, which induces macrophage-like maturation, resulted in a 70% reduction of incorporation of [35S]sulfate into cell-associated glycosaminoglycans. Thus, even in HL-60 cells in which glycosaminoglycan production is maximally stimulated by beta-D-xyloside, TPA is a strong inhibitor of free glycosaminoglycan chain production, and this biochemical effect is associated with other features of leukocyte maturation.
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology*; D009113:Muramidase / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014468:Umbelliferones / Q000494:pharmacology*
D006025:Glycosaminoglycans; D011509:Proteoglycans; D014468:Umbelliferones; D006923:Hymecromone; C014111:methylumbelliferyl-beta-D-xyloside; D009113:Muramidase; D013755:Tetradecanoylphorbol Acetate