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Experimental & Molecular Medicine ; : 214-220, 1998.
Artigo em Inglês | WPRIM | ID: wpr-159767

RESUMO

Human promyelocytic leukemia cells (HL-60) have been used as a model system in which to study the effects of protein phosphatase inhibitors on NADPH-oxidase activation. Since O2- is generated by NADPH-oxidase, we examined the effect of calyculin A pretreatment on oxidase activation in response to various agonists. When Me2SO-differentiated HL-60 cells were treated with calyculin A prior to the addition of phorbol 12-myristate 13-acetate (PMA), O2- production was inhibited; however, calyculin A enhanced O2- production by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The decreased O2- production seen with calyculin A pretreatment followed by PMA may be due to diminished translocation of the p47-phox and p67-phox, cytosolic components of the oxidase, and inhibition of arachidonic acid release. Interestingly calyculin A pretreatment followed by either agonist significantly enhanced mitogen-activated-protein kinase (MAPK) activity. The differential effects of pretreatment with calyculin A on subsequent oxidase stimulation elicited by FMLP or PMA provide further evidence for substantial heterogeneity in the activation of the respiratory burst.


Assuntos
Humanos , Ácido Araquidônico/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Diferenciação Celular , Dimetil Sulfóxido/farmacologia , Inibidores Enzimáticos/farmacologia , Células HL-60 , N-Formilmetionina Leucil-Fenilalanina/farmacologia , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Oxazóis/farmacologia , Oxigênio/metabolismo , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosfoproteínas/imunologia , Transdução de Sinais , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo
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