INVESTIGADORES
SALVADOR Gabriela Alejandra
artículos
Título:
Phosphatidic Acid and Diacylglycerol generation is regulated by Insulin in rat cerebral cortex synaptosomes from adult and aged rats
Autor/es:
GABRIELA A. SALVADOR; MONICA ILINCHETA DE BOSCHERO; SUSANA PASQUARE; NORMA GIUSTO
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
Wiley Interscience
Referencias:
Lugar: Hoboken; Año: 2005 vol. 81 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.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.