Prevention of tubulin/aldose reductase association delays the development ofpathological complications in diabetic rats

SWEDSKY, JULIETA; BRINGAS, LUCRECIA; MARCHISIO MOSCARDO, SOL; SANTANDER, VERÓNICA S.; MONESTEROLO NOELIA E; CAMPETELLI, ALEXIS N.; CASALE, CESAR H.; RIVELLI, JUAN F.

Mendoza

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2022

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

In recent studies, we found that compounds derived from phenolic acids (CAFs) prevent the formation of the tubulin/aldose reductase complex and, consequently, may decrease the occurrence or delay the development of secondary pathologies associated with aldose reductase activation in diabetes mellitus. To verify this hypothesis, we determined the effect of CAFs on Na,K-ATPase tubulin-dependent activity in COS cells, ex vivo cataract formation in rat lenses and finally, to evaluate the antidiabetic effect of CAFs, diabetes mellitus was induced in Wistar rats, they were treated with different CAFs and six parameters were determinants: i-cataract formation, ii- erythrocyte deformability, iii-nephropathy, iv-blood pressure, v-phosphatidylserine exposure in erythrocytes and vi- blood coagulation time. After confirming that CAFs are able to prevent the association between aldose reductase and tubulin, we found that treatment of diabetic rats with these compounds decreased membrane-associated acetylated tubulin, increased NKA activity, and thus reversed the development of six AR-activated complications of diabetes mellitus determined in this work. Based on these results, the existence of a new physiological mechanism is proposed, in which tubulin is a key regulator of aldose reductase activity. This mechanism can explain the incorrect functioning of aldose reductase and Na,K-ATPase, two key enzymes in the pathogenesis of diabetes mellitus. Moreover, we found that such alterations can be prevented by CAFs, which are able to dissociate tubulin/aldose reductase complexes.