Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

Autor(es)

G.B. Peres ^[1] ; M.A. Juliano ^[2] ; J.A.K. Aguiar ^[1] ; Y.M. Michelacci ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 47, n. 6, p. 452-460, 2014-05-09.

Resumo

It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10th or the 30th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver. (AU)

• Processo FAPESP: 10/16022-5 - Enzimas lisossomais, metaloproteinases e proteoglicanos em Diabetes mellitus
• Beneficiário: Yara Maria Corrêa da Silva Michelacci
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/11817-2 - Expressão de enzimas lisossomais e metaloproteases em modelo experimental de diabetes mellitus
• Beneficiário: Giovani Bravin Peres
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/07109-8 - Expressão e atividade de enzimas lisossomais em células renais em cultura expostas a condições que mimetizam o estado diabético
• Beneficiário: Yara Maria Corrêa da Silva Michelacci
• Modalidade de apoio: Auxílio à Pesquisa - Regular