Inhibition of N-linked glycosylation induces early apoptosis in human promyelocytic HL-60 cells.
Inhibition of protein N-glycosylation by tunicamycin induced morphological changes characteristic of apoptosis in human promyelocytic HL-60 cells. Internucleosomal DNA fragmentation could be detected after short-time incubation (between 6 and 9 h) of HL-60 cells with low doses of tunicamycin (0.05 micrograms/ml). Under these conditions the synthesis of glycoproteins was reduced to 17% of control values, while no significant changes in the rates of total protein synthesis could be observed. Tunicamycin ability to induce DNA fragmentation was in good correlation with its potency as glycosylation inhibitor in several myeloid cell lines. Tunicamycin-induced apoptosis was potentiated by activation of protein kinease C (PKC) by phorbol esters and partially prevented by the PKC inhibitor staurosporine. Inhibitors of RNA and protein synthesis displayed a protective effect. Treatment of HL-60 cells with tunicamycin did not elicit the expression of cell surface differentiation antigens or their ability to generate superoxide anion. In contrast, tunicamycin significantly inhibited these processes during dimethyl sulfoxide (DMSO)-induced myeloid differentiation. These observations indicate that the main effect of tunicamycin in HL-60 cells is the induction of apoptosis.
Pérez-Sala
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D
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Mollinedo
F
F
D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D004249:DNA Damage; D004789:Enzyme Activation; D006023:Glycoproteins / Q000096:biosynthesis; D006031:Glycosylation; D006801:Humans; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
D006023:Glycoproteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D014415:Tunicamycin; D011493:Protein Kinase C