ASSOCIATION BETWEEN ALDOSE REDUCTASE AND TUBULIN: EFFECT OF TYROSINE DERIVATIVES.

OCHOA A.N.; RIVELLI ANTONELLI, J.F.; PREVITALI G.; CASALE C.H.

Cordoba

Congreso; 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2016

SAIB

In our laboratory we found that tyrosine inhibits the association between aldose reductase (AR) and tubulin (TUB). causing a decreasein activation of AR by TUB. AR activation is associated with diabetic cataract formation, but the tyrosine is able to prevent this onsetboth in vivo and in ex -vivo models. Our interest was to determine whether tyrosine derived compounds can have the same effect astyrosine on the AR/TUB association. Tyrosine derivatives that have the same basic structure of the molecule with substituents on thecarboxyl, amino and phenolic group of tyrosine were selected for this study. The first study was the determination of the diabeticcataract lenses ex-vivo in mice. Of the seven tested compounds, five decreased, to a greater or lesser degree, the formation of diabeticcataract in lenses treated ex-vivo. Nearly all the derivatives inhibited the AR/TUB association complex. 3-iodo-tyrosine proved to bethe most effective of the tested compounds that, at concentrations as low as 50 µM, prevented diabetic cataract lenses in ex-vivo treatedmice and also interacted directly with AR. These results show the first evidence that tyrosine derivatives are capable of regulating theAR/TUB association and thereby prevent diabetic cataract.