Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells

Abstract

The synthesis of phospholipids in mammalian cells is regulated by the availability of three critical precursor pools: those of choline, cytidine triphosphate and diacylglycerol. Diacylglycerols containing polyunsaturated fatty acids (PUFAs) apparently are preferentially utilized for phosphatide synthesis. PUFAs are known to play an important role in the development and function of mammalian brains. We therefore studied the effects of unsaturated, monounsaturated and polyunsaturated fatty acids on the overall rates of phospholipid biosynthesis in PC12 rat pheochromocytoma cells. Docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6) all significantly stimulated the incorporation of 14 C-choline into total cellular phospholipids. In contrast, monounsaturated oleic acid (OA) and the unsaturated palmitic (PA) and stearic (SA) acids did not have this effect. The action of DHA was concentration-dependent between 5 and 50 μM; it became statistically significant by 3 hrs after DHA treatment and then increased over the ensuing 3 hours. DHA was preferentially incorporated into phosphatidylethanolamine (PE) and phosphatidylserine (PS), while AA predominated in phosphatidylcholine (PC).

Giving Uridine and/or Docosahexaenoic Acid Orally to Rat Dams during Gestation and Nursing Increases Synaptic Elements in Brains of Weanling Pups

“…DHA increases serine incorporation into PS in vitro [Garcia et al, 1998], is preferentially incorporated into PS and PE in PC12 cells [Richardson and Wurtman, 2007], and is enriched in brain PS and PE of adults [Svennerholm, 1968]. Moreover, dietary restriction of omega-3 fatty acids during gestation reportedly decreases PS synthesis brain cortex of newborn rats [Tam and Innis, 2006].…”

Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents

“…These include, among others, changing the “fluidity” of neuronal membranes (11), and thereby alternating the activities of receptors, ion channels, G-proteins, and other proteins embedded in the membranes; being transformed to active metabolites (12) like “neuroprotectin D1” (10,17S-docosatriene) which reportedly suppresses A-beta-42 neurotoxicity (13) or to the prostaglandin-like F4-neuroprostanes (14); promoting neurogenesis by causing the differentiation of neuronal stem cells (15); activating syntaxin-3, a synaptic membrane protein that promotes neurite outgrowth (16); decreasing the AA content of brain phospholipids (17); or forming DHA-rich diacylglycerols which are preferentially utilized for synthesizing membrane phosphatides via the Kennedy Cycle (18). …”

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

“…Although the retinal cell lines have the machinery for VLC-PUFA biosynthesis, we excluded them because they endogenously express relatively higher levels of the ELOVL4 protein, which could affect the interpretation of our results. Because the major pathological phenotype seen in humans with mutations in the ELOVL4 gene is restricted to retinal neurons (photoreceptors), we chose PC12 cells, which are easily differentiated to neuronal cell lineage, can be easily transduced with viral particles, and have been extensively employed as a model system for neuronal differentiation and neuronal FA metabolism ( 56,57 ). The expression profi le of PC12 cell FA elongase and FA desaturase genes involved in VLC-PUFA biosynthesis was determined by using qRT-PCR ( Fig.…”