PHENOLIC ACID PREVENT DIABETIC COMPLICATION ABOLISHING THE ACTIVATION OF ALDOSE REDUCTASE BY TUBULIN

RIVELLI ANTONELLI, J.F.; CASALE C.H.; SANTANDER V.S.; PREVITALI G.

Mar del Plata

Congreso; LXIV Reunion annual de la Sociedad Argentina de Investigacion Clinica (SAIC); 2019

Reunión Anual SAIC ? SAFE ? SAB ? SAP 2019 ? AACyTAL

ABSTRACTPreviously in our laboratory we describe that that the overexpressed and purified human aldose reductase (AR) interacts directly with tubulin, mainly whit the 3-nitro-tyrosinated isotype of α-tubulin, forming a tubulin/AR complex and when this complex is incorporated into a growing microtubule the AR activity is increased more than 6 times. More recently we show that tyrosine (Tyr), 3-nitrotyrosine (Ntyr) and different compounds derived from phenolic acids (CAFs) similar to tyrosine prevent the formation of Tub/AR complex and enzyme activation in vitro. In vivo, in cells in culture in high concentrations of glucose, CFAs prevent the formation of the tubulin/AR complex, the induction of microtubule formation by high concentrations of glucose and the consequent activation of AR and Na+,K+-ATPase (NKA) inhibition by tubulin. These results show that tubulin regulates AR by a direct interaction which can be prevented in vivo and in vitro by CAFs. In this work we investigate in a model of diabetic rats the effect of CAFs Tyr, NTyr and vanilic acid on the development of four secondary complications of diabetes mellitus in which it is recognized for decades the participation of the activation of AR: i) diabetic cataracts, ii) alterations in erythrocyte deformability, iii) development of arterial hypertension and iv) development of renal insufficiency. The results obtained show that Tyr, NTyr and vanilic acid prevent the development of cataracts and increase the survival of diabetic rats, which correlates with better renal functioning, the maintenance of a normal erythrocyte deformability and the prevention of the development of arterial hypertension. Together these data suggest that AR and NKA activity can be controlled in vivo by the association / dissociation of the Tub / AR complex, since CAFs were able to attenuate the development of secondary pathologies of DM due to their preventive action of Tub / AR interaction, preventing the activation of AR and inhibition of NKA.