Prevención de la formación de cataratas diabéticas por inhibición de la formación del complejo Tubulina/Aldosa Reductasa.

RIVELLI A. J., SANTANDER V., MONESTEROLO N., NIGRA A., PREVITALI G., AMAIDEN M., ARCE C., PIE J., CASALE C.

Mar del Plaata

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC) conjuntamente con la Reunión de la Sociedad Argentina de Fisiología (SAFIS) y la XLV Reunión de la Sociedad Argentina de Farmacología Experimental (SAFE); 2013

The major pathogenic pathway in diabetes where by hyperglycemia causes damage in tissues with in sulin-independent glucose transport is activation of the enzyme aldose reductase (AR). AR activation is associated with various complications of diabetes (e.g., cataract formation, retinopathy). No AR inhibitor that combines selectivity, efficacy, andsa fety for human therapeutic application has been found despite>5 decades of research. We demonstrate here, using a diabetic rat model, that AR interacts directly with tubulin (primarilythe3-NTyr-tubisotype) and that consequent AR activation occurs through tubulin polymerization. Free Tyror3-NTyrin hibited tubulin/AR complex formation, AR activation, and various pathological effects induced by high glucose concentrations, including cataract formation. We propose a novel mechanism of NKA and AR regulation by tubulin underhigh-glucose conditions, and show that AR activity can be regulated by drugs that inhibit tubulin/AR association.