Differentiation of HL-60 cells by phorbol ester is correlated with up-regulation of protein kinase C-alpha.
To clarify the mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced macrophage-like differentiation of HL-60 cells, we investigated the correlation between the effects of protein kinase C (PKC) inhibitors on the induction of markers of TPA-induced differentiation and those on suggested critical steps of the differentiation. H-7, sphingosine, and trifluoroperazine significantly suppressed TPA-induced cell adhesion but their effects on the induction of acid phosphatase and nonspecific esterase differed among the inhibitors. The three inhibitors failed to affect on TPA-induced annexin I expression. In contrast, staurosporine markedly suppressed the induction of all these markers. The effects of the inhibitors on some suggested critical steps of the differentiation, a rapid phosphorylation of specific proteins, a rapid membrane association of PKC, and down-regulation of PKC at 18 h after addition of TPA, were not correlated with those on the differentiation marker induction. Only the effect of the inhibitors on up-regulation of PKC-alpha was closely correlated with TPA-induced annexin I expression; staurosporine inhibited up-regulation of PKC-alpha but other inhibitors did not similarly affect the induction of annexin I expression. These results suggest that PKC-alpha is intimately related to macrophage-like differentiation of HL-60 cells by TPA.
Edashige
K
K
Institute for Laboratory Animals, Kochi Medical School, Japan.
Sato
E F
EF
Akimaru
K
K
Kasai
M
M
Utsumi
K
K
D000135:Acid Phosphatase / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D017305:Annexin A1 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D004950:Esterases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D017305:Annexin A1; D010750:Phosphoproteins; D011493:Protein Kinase C; D004950:Esterases; D000135:Acid Phosphatase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate