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Inhibition of N‐linked glycosylation induces early apoptosis in human promyelocytic HL‐60 cells
Author(s) -
PérezSala Dolores,
Mollinedo Faustino
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041630312
Subject(s) - tunicamycin , apoptosis , glycosylation , microbiology and biotechnology , staurosporine , chemistry , glycoprotein , dna fragmentation , cell culture , biology , biochemistry , programmed cell death , protein kinase c , signal transduction , unfolded protein response , genetics
Inhibition of protein N‐glycosylation by tunicamycin induced morphological changes characteristic of apoptosis in human promyelocytic HL‐60 cells. Internu‐cleosomal DMA fragmentation could be detected after short‐time incubation (between 6 and 9 h) of HL‐60 cells with low doses of tunicamycin (0.05 μg/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. © 1995 Wiley‐Liss, Inc.