CORRELAÇÃO DA ATIVIDADE DO PROTEASSOMA, EXPRESSÃO DE CD44 E ENZIMAS PROTEOLÍTICAS EM EXTRATOS INTESTINAIS DE CAMUNDONGOS TRATADOS COM 1,2 DIMETILHIDRAZINA E INIBIDORES BOWMAN-BIRK

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

02/06/2011

RESUMO

The Bowman-Birk inhibitors (BBI) are protein molecules containing two distinct inhibitory domains for trypsin and chymotrypsin-like enzymes. The interest for this class of inhibitors is based on studies which demonstrated a protective effect promoted by BBI, particularly for chemically-induced cancers. In the present work, we evaluated the effects of BBI isolated from Macrotyloma axillare and Glycine max in the prevention of colon cancers induced by intraperitoneal injections of dimethylhydrazine (DMH) during 12 weeks. Control and DMH-treated animals were fed a diet containing BBI at a dose of 0.1% (p/p) associated (DMHV) or not with the vitamins A, C and E, during 24 weeks. DMH-treated animals exhibited hystopathological alterations compatible with the formation of neoplastic polyps. In agreement with the hystological examinations, analysis of the tumor marker CD44, by Western blotting, revealed a significant increase in its expression for the DMH-treated group. Protein extracts from these tissues also contained increased proteasome-dependent proteolytic activity as judged by peptidase assays for the trypsin and chymotrypsin-like activities. In contrast, for DMH + BBI-treated animals proteasomal activity was comparable to that observed for the control group. In fact, animals given BBI alone, as a diet supplement, exhibited decreased proteasomal activity when compared to that from animals fed a normal diet. In addition, by using a sepharose-BBI affinity column, it was observed retention of enzymes displaying trypsin and chymotrypsin-like activities obtained from the lysosomal and soluble fractions. These proteolytic activities were also shown to be increased for DMH-treated animals. These results suggest that the inhibition of distinct proteolytic activities could account for the protective mechanisms produced by BBI. Collectively our analyses allowed us to conclude that BBI treatment was able to prevent intestine polyp formation, decrease any associated inflammatory processes and keep at basal levels the classic tumor marker CD44.

ASSUNTO(S)

expressão de cd44 inibidores bowman-birk bioquimica proteassoma

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