ALDOSE REDUCTASE ACTIVATION AND NA+,K+-ATPase INHIBITION INDUCED BY HIGH GLUCOSE

RIVELLI J.F.; PREVITALI G.; SANTANDER V..S; FERNANDEZ A; ARCE C.A.; CASALE C.H.

Puerto Madryn

Congreso; 46 Annual Meeting Argentine Society for Biochemistry and Molecular Biology - XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

CB-P39 ALDOSE REDUCTASE ACTIVATION AND NA+,K+-ATPase INHIBITION INDUCED BY HIGH GLUCOSE Rivelli JF1, Previtali G1, Santander VS1, Fernandez A1, Arce CA2, Casale CH1 1Dpto. Biologia Molecular. UNRC. 2CIQUIBIC-UNC. E-mail: jrivelli@exa.unrc.edu.ar The association of tubulin with the membrane induced by glucose and sorbitol was determined in COS, CAD and human erythrocytes cells. When these cells was exposed to high levels of glucose or sorbitol was observed: a) association of tubulin to the membrane, b) formation of a complex acetylated tubulin/Na+,K+-ATPase and inhibition of the enzimatic activity, c) microtubule formation, and d) aldose reductase (AR) activation in a dependent-manner of microtubule formation. These effects triggered by high glucose are present in erythrocytes of diabetic patients and different tissue with non-insulin dependent glucose transporters. Na+,K+-ATPase (NKA) activity is reduced by 50 % in membranes of human erythrocytes from diabetic individuals whereas AR activity was increased in a % and the membrane tubulin increase more than 200 % in these individuals. Immunoprecipitation analysis showed that acetylated tubulin forms a complex with NKA in erythrocyte membranes of diabetic humans. These results suggest that glucose trigger a synergistic effect of tubulin and sorbitol, leading to AR activation and NKA inhibition by microtubules formation.