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.
