Age-related changes in the metabolization of phosphatidic acid in rat cerebral  cortex synaptosomes.
In this study, phosphatidic acid (PA) metabolization is found to generate diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol by the sequential action of lipid phosphate phosphatase (LPP), diacylglycerol lipase (DAGL), and monoacylglycerol lipase (MAGL) in cerebral cortex (CC) synaptosomes. It is also demonstrated that PA is metabolized by phospholipases A (PLA)/lysophosphatidic acid phosphohydrolase (LPAPase) in synaptic endings. Age-related changes in the metabolization of PA have been observed in rat cerebral cortex synaptosomes in the presence of the alternative substrates for LPP, namely LPA, sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). In addition, LPA and C1P up to concentrations of about 50 microM favor the metabolism in the direction of MAG and glycerol in aged and adult synaptosomes, respectively. At equimolecular concentrations with PA, LPA decreases DAG formation in adult and aged synaptosomes, whereas S1P decreases it and C1P increases it only in aged synaptosomes. Sphingosine (50 microM) or ceramide (100 microM) increase PA metabolism by the pathway that involves LPP/DAGL/MAGL action in aged membranes. Using RHC-80267, a DAGL inhibitor, we could observe that 50% and 33% of MAG are produced as a result of DAGL action in adult and aged synaptosomes, respectively. Taken together, our findings indicate that the ageing modifies the different enzymatic pathways involved in PA metabolization.
Pasquaré
S J
SJ
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C.C. 857, B8000FWB Bahía Blanca, Argentina. pasquare@criba.edu.ar
Gaveglio
V L
VL
Giusto
N M
NM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003512:Cyclohexanones / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D050178:Monoglycerides / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
C011439:1,2-diacylglycerol; D002518:Ceramides; D003512:Cyclohexanones; D004075:Diglycerides; D008246:Lysophospholipids; D050178:Monoglycerides; D011480:Protease Inhibitors; C065576:ceramide 1-phosphate; C060506:sphingosine 1-phosphate; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D008071:Lipoprotein Lipase; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase; D013110:Sphingosine; D005990:Glycerol; C032881:lysophosphatidic acid