Retinoic acid modifies lipid metabolism in isolated adult and aged rat cerebellum nuclei

Abstract

Nuclear lipid metabolism gives rise to several lipid second messengers that seem to be involved in the regulation of nuclear structure and gene expression. The purpose of the present research was therefore to study the metabolic pathways involved in the metabolism of phosphatidic acid (PA) and its regulation in isolated nuclei from the central nervous system. This study was also conducted in isolated nuclei from aged animals allowing us to analyze the effects of neurodegeneration processes on PA metabolism as a result of ageing. Adult (4 mo) and aged (28 mo) rat cerebellums were homogenized and highly purified nuclei were isolated by sucrose-density ultracentrifugation. Using radiolabelled substrates we demonstrated lipid phosphate phosphatases (LPPs), diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL), lysophosphatidate phosphohydrolase (LPAPase) and phospholipase (LPAase) as well as PA-phospholipase type A (PLA) activities. We further studied their regulation by the nuclear agonist retinoic acid (RA), which was observed to decrease DAGL and MAGL activities. Significant aged-related changes in the above-mentioned enzymatic activities as well as in its regulation by RA were observed. Taken together, our results demonstrate a RA-regulated PA metabolism in rat cerebellum nuclei which could be involved in neurodegeneration processes.