ENTRY OF POLYUNSATURATED FATTY ACIDS INTO THE BRAIN - EVIDENCE THAT HIGH-DENSITY LIPOPROTEIN-INDUCED METHYLATION OF PHOSPHATIDYLETHANOLAMINE AND PHOSPHOLIPASE A(2) ARE INVOLVED

摘要

The conversion of phosphatidylethanolamine (PE) phosphatidylcholine (PC) by a sequence of three methylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL(3)) in isolated bovine brain capillary (BBC) membranes. HDL(3)-induced stimulation of BBC membranes pulsed with [methyl-C-14]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC, PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A(2) (PLA(2)), as demonstrated by the accumulation of lysophosphatidylcholine (lyse-PC). When PE containing [C-14]arachidonic acid in the sn-2 position ([C-14]PAPE) is incorporated into BBC membranes, HDL, stimulation induces the formation of PMME, PDME, PC and lyse-PC and the release of [C-14]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL(3) stimulates a PLA(2) that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA(2) activities depend on a HDL(3) concentration in the range 0-50 mu g/ml and are strictly dependent on HDL(3) binding, because HDL(3) modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA(2) activation, Moreover, HDL(3) prelabelled with [C-14]PAPE can stimulate PDME and lyse-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL(3) can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL(3) binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.