Aldose Reductase activation and Na+,K+-ATPase inhibition by increase of microtubules content induced by high glucose.

RIVELLI JF; PREVITALI G; SANTANDER VS,; FERNANDEZ A; CASALE CH

Puerto Madryn

Congreso; SAIB 2010; 2010

SAIB

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.