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

OCHOA AL; RIVELLI JF; G PREVITALI; C H CASALE.

Congreso; saib 2016; 2016

Inour laboratory we found that tyrosine inhibits the association between aldosereductase (AR) and tubulin (TUB). causing a decrease in activation of AR byTUB. AR activation is associated with diabetic cataract formation, but thetyrosine is able to prevent this onset both in vivo and in ex vivo models. Ourinterest was to determine whether tyrosine derived compounds can have the sameeffects as tyrosine on the AR/TUB association. Tyrosine derivatives that havethe same basic structure of the molecule with substituents on the carboxyl,amino and phenolic group of tyrosine were selected for this study. The firststudy was the determination of the diabetic cataract lenses ex-vivo in mice. Of the seven testedcompounds, five decreased, to a greater or lesser degree, the formation ofdiabetic cataract in lenses treated ex-vivo.Nearly all the derivatives inhibited the AR/TUB association complex.  3-iodo-tyrosine proved to be the mosteffective of the tested compounds that at concentrations as low as 50 µMprevented diabetic cataract lenses ex-vivotreated mice and also interacted directly with AR. These results show the firstevidence that tyrosine derivatives are capable of regulating the AR/TUBassociation and thereby prevent diabetic cataract.