Insulin modifies aging-related inhibition of 1-stearoyl, 2-achidonoylglycerol phosphorylation in rat synaptic terminals.

ZULIAN S.E.; ILINCHETA DE BOSCHERO M.G.; GIUSTO N.M.

NEUROCHEMISTRY INTERNATIONAL

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 58 p. 330 - 336

0197-0186

The purpose of the present study was to analyze diacylglycerol kinase (DAGK) activity in synapticterminals fromcerebral cortex (CC) and hippocampus (Hp) fromadult (3–4month-old) and aged (26–28month-old) rats. The effect of insulin through DAGK activity on synaptosomes from adult and aged ratswas also analyzed under conditions favoring saturated or unsaturated phosphatidic acid (PA) formation,using exogenous di-palmitoil glycerol (DPG) or 1-stearoyl-2-arachidonoylglycerol (SAG) as substrates.Results showed that the enzymatic activity preferentially uses SAG as substrate, thus indicating thepresence of e-type DAGK. A significant decrease in DAGK activity transforming SAG into PA was alsoobserved in both tissues from aged rats.Western blot detection of DAGKe showed that enzyme contentundergoes no changes with aging.[3H] inositol incorporation into phosphoinosites was also analyzed to evaluate the role of DAGKe intheir synthesis. Data obtained from 3H-inositol incorporation into phosphoinositides revealed that insynaptosomes from aged rats phosphatidylinositol (PI) synthesis is lower than in adult animals.Interestingly, in the presence of SAG, PI synthesis was restored to adult values.DAGK activity over SAG was more highly stimulated by insulin in CC and Hp synaptosomes of agedrats with respect to adult rats. On the other hand, insulin exerted a stimulatory effect on PI andphosphatidylinositol 4 phosphate (PI(4)P) synthesis in synaptosomal CC from aged rats. Taken together,our findings indicate that in aged rats insulin triggers a stimulatory mechanism that reverts thediminished synaptosomal ability to synthesize arachidonoyl phosphatidic acid (20:4 PA). The recovery ofthis PA species indicates that insulin positively regulates phosphoinositide synthesis. 2010 Elsevier Ltd. All rights reserved.