Relação entre a atividade da proteina tirosina fosfatase e a ação citotoxica de antimalaricos sobre linfocitos humanos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

The aim of this work was to verify the effect of antimalarial drugs in phosphatases isolated from human Iymphocytes and the action of these pharmaceutical drugs on Iymphocytes viability. Phosphatase activity was determined through the pnitrophenol assay and cell viability through 3 parameters: MTT reduction (mitochondrial integrity), protein content (cell number index) and phosphatase activity (cell metabolism). Phosphatases from membrane and cytoplasm were not affected by chloroquine. However, an inhibitory effect on cytoplasmic phosphatases (30%) on total fraction (25%) was observed after pre-incubation of the enzyme in presence of the quinine. In contrast to other antimalarials desferoxamine, the phosphatases actived from the total fraction and membrane, 40 and 70%, respectively. In the citotoxicity studies, chloroquine showed low citotoxicity when the activity of total phosphatase (IC50=360_M) and protein content (IC50=346_M) were analysed, when compared to the toxicity observed with MTT test (IC50=75_M). Quinine also had a high toxicity for the mitochondria (130% increased MTT the reduction), when compared to protein quantification and phosphatase activity (40% inhibition). Our results suggest that the cytotoxic action of antimalarials (quinine and chloroquine) can be due to two factors: direct inhibition of protein phosphatases, since kinetic studies had shown that the predominant phosphatases in Lymphocytes are protein tyrosine phosphatases and protein serine/treonine phosphatases or inhibition of sulfhydryl group dependent enzymes and alteration of organelas such as mitochondria by inducing oxidative stress. Desferoxamine had an activator action in membrane protein phosphatases of, probably acting on the CD45. Antioxidant substances (GSH and ascorbic acid) caused activation of phosphatases, but, in presence of quinine, cloroquine and desferoxamine this activation was more significative

ASSUNTO(S)

linfocitos fosfatases antimalaricos

ACESSO AO ARTIGO

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