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

RIVELLI, JUAN F. ; SANTANDER, VERONICA S.; NIGRA, AYELEN D. ; MONESTEROLO, NOELIA E.; PREVITALI, GABRIELA; PRIMO, EMILIANO D.; OTERO, LISANDRO H.; CASALE, CESAR H.

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY

SERVICIO PUBLICACIONES UNIVERSIDAD NAVARRA

Lugar: Navarra; Año: 2021 vol. 77 p. 565 - 576

1138-7548

In recent studies, we found that compounds derived from phenolic acids (CAFs) prevent the formation of the tubulin/aldosereductase complex and, consequently, may decrease the occurrence or delay the development of secondary pathologies associ-ated 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 antidiabeticeffect of CAFs, diabetes mellitus was induced in Wistar rats, they were treated with different CAFs and four parameters weredeterminates: cataract formation, erythrocyte deformability, nephropathy and blood pressure. After confirming that CAFs areable to prevent the association between aldose reductase and tubulin, we found that treatment of diabetic rats with thesecompounds decreased membrane-associated acetylated tubulin, increased NKA activity, and thus reversed the development offour AR-activated complications of diabetes mellitus determined in this work. Based on these results, the existence of a newphysiological mechanism is proposed, in which tubulin is a key regulator of aldose reductase activity. This mechanism canexplain the incorrect functioning of aldose reductase and Na + ,K + -ATPase, two key enzymes in the pathogenesis of diabetesmellitus. Moreover, we found that such alterations can be prevented by CAFs, which are able to dissociate tubulin/aldosereductase complex.