Regulation of phosphatidic acid metabolism by different nuclear agonists in isolated nuclei from rat cerebellum

GAVEGLIO, V.L.; PASCUAL, A.C.; GIUSTO, N.M.; PASQUARÉ, S.J.

Bari

Conferencia; 54 th International Conference on the Bioscience of Lipids (ICBL); 2013

Nuclear lipid metabolism gives rise to several lipid second messengers and signaling molecules that seem to be involved in the regulation of nuclear structure and gene expression. The purpose of the present research was to study the metabolic pathways involved in the metabolism of phosphatidic acid (PA) and its regulation by different agonists in isolated nuclei from the central nervous system. Adult (4 mo) rat cerebellums were homogenized and highly purified nuclei were isolated by sucrose-density ultracentrifugation. Purity was checked by electron microscopy and subcellular marker enzymatic activities. Using radiolabelled substrates we demonstrated the presence of lipid phosphate phosphatase, diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) activities in isolated nuclei. We focused our study on the regulation of these enzymatic activities by retinoic acid (RA), lysophosphatidic acid (LPA) and prostaglandin E2 (PGE2), as their receptors have been described at nuclear level. Significant changes in the above-mentioned enzymatic activities were observed. LPA (10 μM) increased DAG while decreased MAG production in a similar percentage (15%), thus indicating an inhibition in DAGL activity. Furthermore, RA (10 μM) significantly inhibited DAGL (75%) and MAGL (29%) activities while PGE2 modified none of these enzymes. Taken together, our results demonstrate a regulated PA metabolism in rat cerebellum nuclei which could be involved in gene expression and transcription processes.