Metabolización de endocanabinoides por monoacilglicérido lipasa en sistema nervioso central

GAVEGLIO, V.L., PASQUARÉ, S.J. Y GIUSTO, N.M

Mar del Plata

Congreso; LII Reunión de la Sociedad Argentina de Investigación Clínica; 2007

Sociedad Argentina de Investigación Clínica

Evidences not only confirm the presence of lipids in the nucleus as a part of the chromatin structure but also demonstrate the existence of numerous enzymes which modulate changes in their composition. Phosphatidic acid (PA) is metabolized to diacylglycerol (DAG) by PAP1 and LPPs. DAGs are partially metabolized to monoacylglycerols (MAG) by diacylglyceride lipase (DGLs) activities, and MAG are metabolized to water soluble products (WSP) by MAGL activities. LPPs dephosphorylate PA, lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). The aim of the present work was to evaluate which PAP isoforms are associated to liver nuclei and how PAis metabolized by LPPs in the presence of LPA, S1P and C1P. To this purpose, adult (4 mo) rat liver was homogenized and highly purified nuclei were isolated by sucrose-density ultracentrifugation. Nuclear preparations were checked for purity by electron microscopy. Our results indicate that LPPs are present in nuclei from liver. In addition, it was observed that nuclear DGL and MAGL activities represent 70% and 28% of LPPs activities, respectively.At equimolecular concentrations (100 M) of PA/LPA or PA/S1P, LPPs diminished PA metabolization by 25% and 21%, respectively. PA metabolization in nuclei by LPPs seems to be an important signalling pathway in this fraction.