INVESTIGADORES
GIUSTO Norma Maria
artículos
Título:
Posphatidic acid and diacylglycerol generation is regulated by Insulin in cerebral cortex synaptosomes from adul and aged rats
Autor/es:
G A SALVADOR,; M G ILINCHETA DE BOSCHERO,; S J PASQUARÉ,; NORMA MARIA GIUSTO
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
wILEY iNTERNATIONAL
Referencias:
Lugar: NEW jERSEY; Año: 2005 vol. 2 p. 244 - 252
ISSN:
0360-4012
Resumen:
Insulin receptor associated with the cerebral cortex (CC) has been shown
to be involved in brain cognitive functions. Furthermore, deterioration
of insulin signaling has been associated with age-related brain
degeneration. We have reported previously that aging stimulates
phospholipase D/phosphatidate phosphohydrolase 2 (PLD/PAP2) pathway in
CC synaptosomes from aged rats, generating a differential availability
of their reaction products: diacylglycerol (DAG) and phosphatidic acid
(PA). The aim of this work was to determine the effect of aging on DAG
kinase (DAGK), as an alternative pathway for PA generation, and to
evaluate the effect of insulin on PLD/PAP2 pathway and DAGK. PLD, PAP2,
and DAGK activities were measured using specific radiolabeled substrates
in CC synaptosomes from adult (4 months old) and aged rats (28 months
old). In adult animals, in the presence of the tyrosine phosphatase
inhibitor (sodium o-vanadate), insulin stimulated PLD activity
at 5 min incubation. DAGK activity was also increased at the same time
of incubation and PAP2 was inhibited. In aged animals, PLD activity was
not modified by the presence of insulin plus vanadate, PAP2 was
inhibited, and DAGK was stimulated by the hormone. Insulin, vanadate,
and the combination of both induced protein tyrosine phosphorylation in
adult CC synaptosomes. Aged rats showed a lower level of protein
phosphorylation with respect to adult rats. Our results show that
insulin modulates PA and DAG availability through the regulation of
PLD/PAP2 and DAGK pathways in adult rat CC synaptosomes. Additionally,
we demonstrated that PA and DAG generation is regulated differentially
by insulin during aging.