Ethanolamine Phosphoglycerides Research Articles

Phorbol ester stimulates ethanolamine release from the metastatic basal prostate cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6.

Background:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium.Methods:Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were labelled with [1-3H]-Etn hydrochloride. PKC was activated with phorbol ester (TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD (phospholipase D). [3H]-labelled Etn metabolites were resolved by ion-exchange chromatography. Sodium oleate and mastoparan were tested as activators of PLD2. Phospholipase D activity was measured by a transphosphatidylation reaction. Cells were treated with ionomycin to raise intracellular Ca2+ levels.Results:Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to the medium. Phorbol ester treatment over 3h increased Etn metabolite release from the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a transphosphatidylation reaction. Only metastatic PC3 cells specifically upregulated Etn release in response to TPA treatment. Oleate and mastoparan increased GPEtn release from all cell lines at the expense of Etn. Ionomycin stimulated GPEtn release from benign PNT2C2 cells but not from cancer-derived cell lines P4E6 or PC3. Ethanolamine did not stimulate the proliferation of LNCaP or PC3 cell lines but decreased the uptake of choline (Cho).Conclusions:Only the metastatic basal PC3 cell line specifically increased the release of Etn on TPA treatment most probably by PKC activation of PLD1 and increased turnover of EtnPGs. The phosphatidic acid formed will maintain a cancer phenotype through the regulation of mTOR. Ethanolamine released from cells may reduce Cho uptake, regulating the membrane PtdEtn:PtdCho ratio and influencing the action of PtdEtn-binding proteins such as RKIP and the anti-apoptotic hPEBP4. The work highlights a difference between LNCaP cells used as a model of androgen-dependent early stage PCa and androgen-independent PC3 cells used to model later refractory stage disease.

Dimethyl acetals, an indirect marker of the endogenous antioxidant plasmalogen level, are reduced in blood lipids of Sudanese pre-eclamptic subjects whose background diet is high in carbohydrate

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Linoleic acid is associated with lower long-chain n–6 and n–3 fatty acids in red blood cell lipids of Canadian pregnant women

Arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids are important in membrane glycerophospholipids. Higher maternal blood ARA, EPA, and DHA concentrations in gestation are associated with higher maternal-to-fetal transfer of ARA, EPA, and DHA, respectively, which emphasizes the importance of maternal fatty acid status in gestation. As in the brain, red blood cell (RBC) ethanolamine phosphoglycerides (EPGs) are high in plasmalogen, ARA, and DHA. We determined the relation between dietary n-6 (omega-6) and n-3 (omega-3) fatty acid intakes and n-6 and n-3 fatty acids in RBC EPGs and phosphatidylcholine in near-term pregnant women. The subjects were 105 healthy Canadian pregnant (36 wk gestation) women. Fatty acid intakes were estimated by food-frequency questionnaire, and fasting venous blood samples were collected. DHA and EPA intakes were positively associated with RBC EPG and phosphatidylcholine concentrations of DHA (rho = 0.309 and 0.369, respectively; P < 0.001) and EPA (rho = 0.391 and 0.228, respectively; P < 0.001) and inversely associated with RBC EPG 22:4n-6 and 22:5n-6 (P < 0.001). In RBCs, concentrations of linoleic acid (LA, 18:2n-6) were inversely associated with DHA, EPA, and ARA, respectively, in EPGs (r = -0.432, P < 0.01; r = -0.201, P < 0.04; and r = -0.303, P < 0.01) and phosphatidylcholine (r = -0.460, -0.490, and -0.604; P < 0.01 for all). Membrane fatty acids are influenced by the amount and balance of fatty acid substrates. Our results suggest the competitive interaction of LA with ARA, EPA, and DHA, with no evidence that higher LA increases ARA. Biochemical indicators to suggest that DHA is limiting are present in our population. This trial was registered at clinicaltrials.gov as NCT00620672.

Cerebrospinal fluid cholesterols and phospholipids in multiple sclerosis.

Lipids were extracted from cerebrospinal fluid (CSF) samples from 46 patients with multiple sclerosis (MS). Unesterified and esterified cholesterol, total phospholipid, sphingomyelin, choline phosphoglyceride, and ethanolamine phosphoglyceride were separated by thin layer chromatography and determined quantitatively. CSF cholesterol and phospholipid concentrations were correlated with CSF protein concentrations. The mean concentrations of phospholipids were decreased in MS. The relative concentration of esterified cholesterol was increased and that of ethanolamine phosphoglyceride decreased in this disease. Low concentrations predominated in patients with latent probable MS and in patients with slight or no disability. Patients with a recent exacerbation of symptoms and the most severely disabled patients showed a relative increase of esterified cholesterol and a decrease of ethanolamine phosphoglyceride, but these findings were not significant. It is discussed, whether these alterations may be a CSF reflection of changes of CNS lipid composition and metabolism in MS. From a clinical point of view, the determination of CSF cholesterol and phospholipid concentrations seems to be of little help due to the great variation in the concentrations in normal persons and in patients with MS.

Cerebrospinal fluid phospholipids. Quantitative determination of fractionated phospholipids and normal values in the cerebrospinal fluid.

Cerebrospinal fluid (CSF) lipids were extracted, subjected to thin-layer chromatography and quantitative determination of total and fractionated phospholipids. The methods were tested by analysis of serum and CSF pools. In CSF, sphingomyelin, choline phosphoglyceride and ethanolamine phosphoglyceride were isolated and quantitated while in serum further lyso-choline phosphoglyceride was determined. In a “normal” material of 46 patients, with disorders which were not thought to influence the composition of CSF, the total phospholipid phosphorus concentration averaged 168 μMg per 1 CSF. Sphingomyelin, choline phosphoglyceride, and ethanolamine phosphoglyceride accounted for 25, 70 and 5 per cent respectively. The sum of the fractions comprised 93 per cent of total phospholipid phosphorus found. Grouping according to sex and age did not reveal significant differences. A significant correlation was present between CSF phospholipid and protein concentrations.

Cerebrospinal fluid cholesterols and phospholipids in phenylketonuria.

Cerebrospinal fluid (CSF) cholesterols and phospholipids were fractionated and quantitated in 64 patients with phenylketonuria (PKU). In 56 patients the results were related to clinical neurological signs and to the intellectual deficiency. PKU patients had decreased mean concentrations of esterified cholesterol, total phospholipid, sphingomyelin, and choline phosphoglyceride, and increased concentration of ethanolamine phosphoglyceride. The cholesterol but not phospholipid concentrations were significantly correlated to CSF protein concentrations. Decreased cholesterol and phospholipid concentrations were predominantly seen in patients with abnormal motor signs, and the decrease was greatest in the most affected patients. There was no relation between reduced CSF lipid concentrations and the occurrence of epilepsy or the degree of mental deficiency. The reduction of CSF cholesterol and phospholipid concentrations is probably related to myelin abnormalities, and the different results observed in relation to the neurological abnormalities and to the mental deficiency point to a difference in the pathogenesis of these disorders.

Genetic Variants of the FADS1 FADS2 Gene Cluster Are Associated with Altered (n-6) and (n-3) Essential Fatty Acids in Plasma and Erythrocyte Phospholipids in Women during Pregnancy and in Breast Milk during Lactation

The enzymes encoded by fatty acid desaturase (FADS) 1 and FADS2 are rate-limiting enzymes in the desaturation of linoleic acid [LA; 18:2(n-6)] to arachidonic acid [ARA; 20:4(n-6)], and α-linolenic acid [ALA; 18:3(n-3)] to eicosapentaenoic acid [EPA; 20:5(n-3)] and docosahexaenoic acid [DHA; 22:6(n-3)]. ARA, EPA, and DHA play central roles in infant growth, neural development, and immune function. The maternal ARA, EPA, and DHA status in gestation influences maternal-to-infant transfer and breast milk provides fatty acids for infants after birth. We determined if single nucleotide polymorphisms in FADS1 and FADS2 influence plasma phospholipid and erythrocyte ethanolamine phosphoglyceride (EPG) (n-6) and (n-3) fatty acids of women in pregnancy or their breast milk during lactation. We genotypedrs174553, rs99780,rs174575, andrs174583 in the FADS1 FADS2 gene cluster and analyzed plasma and erythrocyte fatty acids and dietary intake for 69 pregnant women and breast milk for a subset of 54 women exclusively breast-feeding at 1 mo postpartum. Minor allele homozygotes ofrs174553(GG), rs99780(TT), andrs174583(TT) had lower ARA but higher LA in plasma phospholipids and erythrocyte EPG and decreased (n-6) and (n-3) fatty acid product:precursor ratios at 16 and 36 wk of gestation. Breast milk fatty acids were influenced by genotype, with significantly lower 14:0, ARA, and EPA but higher 20:2(n-6) in the minor allele homozygotes ofrs174553(GG), rs99780(TT), andrs174583(TT) and lower ARA, EPA, 22:5(n-3), and DHA in the minor allele homozygotes G/G of rs174575. We showed that genetic variants of FADS1 and FADS2 influence blood lipid and breast milk essential fatty acids in pregnancy and lactation.

Patients with Sickle Cell Disease have Reduced Blood Antioxidant Protection

In previous studies, we found that homozygous sickle cell (HbSS) patients, compared with their healthy (HbAA) counterparts, had reduced levels of the omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, in red cells, platelets, and mononuclear cells. These differences were not due to lower intake of the two fatty acids. We have investigated whether reduced antioxidant status in the patients could help explain the observed phenomenon. Blood specimens previously obtained for fatty acid study from Nigerian (26 HbSS and 30 HbAA) and British (30 HbSS, 9 sickle cell-hemoglobin C/HbSC, and 15 HbAA) subjects were analyzed for antioxidant status. The Nigerian HbSS patients compared with the controls had lower plasma retinol, alpha-tocopherol, and beta-carotene concentrations (p < 0.005) and reduced activity of red cell Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (p < 0.05). Similarly, the British HbSS group had reduced concentrations of plasma alpha-tocopherol (p < 0.005), and activities of red cell Cu/Zn-superoxide dismutase (p < 0.05) and Se-glutathione peroxidase (Se-GPx) (p < 0.005) than the controls. In addition, the British patients in comparison with those who had HbSC, a mild form of the disease, had lower alpha-tocopherol than that of the HbAA controls (p < 0.005). In the British sickle cell patients, there was a positive correlation between red cell ethanolamine phosphoglyceride (EPG) DHA and Cu/Zn-SOD activity (r = 0.700, p < 0.05), choline phosphoglyceride (CPG) DHA and Se-GPx activity (r = 0.605, p < 0.05), and CPG EPA and Se-GPx activity (r = 0.558, p > 0.05). Similarly, the percent DHA in red cell EPG was positively related with the activity of Se-GPx in the patients with HbSC (r = 0.674, p < 0.05). These findings suggest that the lower levels of membrane EPA and DHA in blood cells of the HbSS patients could be due to peroxidation resulting from a compromised antioxidant competence.

Lipidomic analysis and electron transport chain activities in C57BL/6J mouse brain mitochondria

The objective of this study was to characterize the lipidome and electron transport chain activities in purified non-synaptic (NS) and synaptic (Syn) mitochondria from C57BL/6J mouse cerebral cortex. Contamination from subcellular membranes, especially myelin, has hindered past attempts to accurately characterize the lipid composition of brain mitochondria. An improved Ficoll and sucrose discontinuous gradient method was employed that yielded highly enriched mitochondrial populations free of myelin contamination. The activities of Complexes I, II, III, and II/III were lower in Syn than in NS mitochondria, while Complexes I/III and IV activities were similar in both populations. Shotgun lipidomics showed that levels of cardiolipin (Ptd(2)Gro) were lower, whereas levels of ceramide and phosphatidylserine were higher in Syn than in NS mitochondria. Coenzyme Q(9) and Q(10) was also lower in Syn than in NS mitochondria. Gangliosides, phosphatidic acid, sulfatides, and cerebrosides were undetectable in brain mitochondria. The distribution of Ptd(2)Gro molecular species was similar in both populations and formed a unique pattern, consisting of seven major molecular species groups, when arranged according to mass to charge ratios. Remodeling involving choline and ethanolamine phosphoglycerides could explain Ptd(2)Gro heterogeneity. NS and Syn mitochondrial lipidomic heterogeneity could influence energy metabolism, which may contribute to metabolic compartmentation of the brain.

Essential n−3 fatty acids in pregnant women and early visual acuity maturation in term infants

Background: Docosahexaenoic acid (DHA) is important to neural development. Whether DHA intakes are low enough in some pregnant women to impair infant development is uncertain.Objective: We sought to determine whether DHA deficiency occurs in pregnant women and contributes to poor infant development.Design: Biochemical cutoffs, dietary intakes, or developmental scores indicative of DHA deficiency are not defined. Infant development has a distribution in which an individual's potential development is unknown. This was a randomized intervention to establish a distribution of developmental scores for infants of women with DHA intakes considered to be above requirements against which to compare the development of infants of mothers consuming their usual diet. DHA (400 mg/d; n = 67) or a placebo (n = 68) was consumed by the women from 16 wk gestation until delivery. We determined maternal red blood cell ethanolamine phosphoglyceride fatty acids, dietary intakes at 16 and 36 wk gestation, and infant visual acuity at 60 d of age.Results: We described an approach to identify DHA deficiency when biochemical and functional markers of deficiency are unknown. In multivariate analyses, infant visual acuity was related to sex (β = 0.660, SE = 0.93, and odds ratio = 1.93) and maternal DHA intervention (β = 1.215, SE = 1.64, and odds ratio = 3.37). More infant girls in the placebo than in the DHA intervention group had a visual acuity below average (P = 0.048). Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was inversely related to visual acuity in boys (ρ = −0.37, P < 0.05) and girls (ρ = −0.48, P < 0.01).Conclusions: These studies suggest that some pregnant women in our study population were DHA-deficient.

Docosahexaenoic acid synthesis from n‐3 fatty acid precursors in rat hippocampal neurons

Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid in the brain, has important functions in the hippocampus. To better understand essential fatty acid homeostasis in this region of the brain, we investigated the contributions of n-3 fatty acid precursors in supplying hippocampal neurons with DHA. Primary cultures of rat hippocampal neurons incorporated radiolabeled 18-, 20-, 22-, and 24-carbon n-3 fatty acid and converted some of the uptake to DHA, but the amounts produced from either [1-14C]alpha-linolenic or [1-14C]eicosapentaenoic acid were considerably less than the amounts incorporated when the cultures were incubated with [1-14C]22:6n-3. Most of the [1-14C]22:6n-3 uptake was incorporated into phospholipids, primarily ethanolamine phosphoglycerides. Additional studies demonstrated that the neurons converted [1-14C]linoleic acid to arachidonic acid, the main n-6 fatty acid in the brain. These findings differ from previous results indicating that cerebral and cerebellar neurons cannot convert polyunsaturated fatty acid precursors to DHA or arachidonic acid. Fatty acid compositional analysis demonstrated that the hippocampal neurons contained only 1.1-2.5 mol% DHA under the usual low-DHA culture conditions. The relatively low-DHA content suggests that some responses obtained with these cultures may not be representative of neuronal function in the brain.

Docosahexaenoic acid‐dependent iron accumulation in oligodendroglia cells protects from hydrogen peroxide‐induced damage

Iron, a transition metal and essential nutrient, is a typical pro-oxidant forming free radicals, lipid peroxides and causing cell damage when added at high (> or = 50 microM) concentrations to oligodendroglia-like OLN-93 cells that have been enriched for 3 days with 10 microM docosahexaenoic acid (DHA, 22 : 6 n-3). At low (5 microM) iron concentrations lipid peroxides were still formed, but cells turned resistant to 250 microM H2O2, a secondary genotoxic stress. This has been attributed most likely to a time-dependent (16 h preconditioning) increase of cellular antioxidant enzyme activities i.e., glutathione peroxidase (38%) and glutathione reductase (26%). DHA but not arachidonic acid (20 : 4 n-6) supplements induced 3-fold increase in gene expression of divalent metal transporter-1, a transporter protein presumably responsible for the increase in intracellular iron. Elevated iron levels triggered a transient scrambling of membrane lipid asymmetry as evident by an accelerated ethanolamine phosphoglyceride translocation to the outer cell surface. Ethanolamine phosphoglyceride reorientation is proposed to activate certain signaling cascades leading to changes in nuclear transcription, a reaction that could represent a mechanism of preconditioning. These findings may have important implications for understanding the interactive role of iron and DHA in nutritional deficiencies, losses of polyunsaturated fatty acids in the aging brain or excessive iron accumulation in degenerative disorders.

Postnatal development of phospholipids and their fatty acid profile in rat heart

The aim of this study was to determine the concentration of phospholipids (PL), plasmalogen components of choline (PC) and ethanolamine (PE) phosphoglycerides (PLPC, PLPE) and fatty acid profile of PL and triacylglycerols (TAG) in developing rat left ventricular myocardium between postnatal day (d) 2 and 100. The steepest increase of total PL (TPL) concentration occurs between d2 and d5, followed by a further slower increase between d20 and d40. Similar developmental changes were observed in PC and PE. The PLPE concentration rises by d10, whereas PLPC does not change during the whole period investigated, except for the transient decline on d5. The concentration of diphosphatidylglycerol (DPG) increases by d60; the steepest rise occurs between d20 and d40. Phosphatidylinositol (PI) concentration rises only by d5. The concentration of phosphatidylserine (PS) decreases between d5 and d10 and then it does not change. Sphingomyelin (SM) concentration is maintained till d10, it declines on d20 and does not change thereafter. The proportion of saturated fatty acids (SFA) increases by d5 in PC, PE, PS and TAG, and by d10 in DPG and PI. After d20 the SFA proportion gradually decline in all lipids. Monounsaturated FA (MUFA) proportion decreases in PC, PE, PI and PS from d2 till d10, and in the weaning period it tends to rise again. In contrast, in DPG and TAG the proportion of MUFA declines during the whole postnatal period. N-6 polyunsaturated FA (PUFA) decrease in all PL by d20 and rise again thereafter; in TAG they decline between d2 and d10 and return to the initial level by d100. N-3 PUFA increase in all PL during the suckling period and decline after weaning; in TAG they increase only by d5 and then they decline. This remodeling of myocardial PL and TAG composition during postnatal development may affect membrane properties and contribute to developmental changes in the function of membrane proteins and cell signaling.

Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids

In previous studies, we reported that neonates of women with gestational diabetes mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA and DHA are selectively transferred from maternal to fetal circulation by the placenta, we have investigated whether the FA composition of the placenta is altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from Newham General Hospital, London. The women with GDM had higher levels of di-homo-gamma-linolenic (P < 0.05), docosatetraenoic (n-6 DTA; P< 0.0001), docosapentaenoic n-6 (P< 0.005), total n-6 (P < 0.005), docosapentaenoic (n-3 DPA; P < 0.005), and total n-3 (P < 0.01) FA, as well as higher levels of AA (P < 0.05) and DHA (P < 0.01), in placental choline phosphoglycerides (CPG) compared with the healthy women who served as controls. Similarly, the women with GDM had elevated n-6 DTA (P < 0.005), AA, total n-6 metabolites (P < 0.05), DHA, total n-3 metabolites, and total n-3 FA (P < 0.005) in ethanolamine phosphoglycerides (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had higher linoleic acid (P< 0.05) and lower AA, n-6 metabolites, and n-3 DPA (P < 0.01). The placenta is devoid of desaturase activity, and it is thought to be reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels of the two FA in the placenta of the GDM group suggests that these FA are taken up from the maternal circulation and retained after esterification into phosphoglycerides instead of being transferred to the fetus. Further study is needed to elucidate the mechanism involved and the effect of the phenomenon on postnatal growth and development of the offspring.

Vitamin A deficiency enhances docosahexaenoic and Osbond acids in liver of rats fed an α‐linoleic acid‐adequate diet

The synthesis of docosahexaenoic (DHA, 22:6n-3) and Osbond acid (OA, 22:5n-6) is regulated by the heterodimer of peroxisome proliferator-activated receptor and retinoid X receptor (RXR). 9-Cis retinoic acid, a metabolite of vitamin A, is the most potent ligand of RXR. We tested whether vitamin A deficiency impairs DHA and OA synthesis in rats fed a vitamin A- and alpha-linolenic acid (ALA)-sufficient (VASALAS), vitamin A-sufficient and ALA-deficient (VASALAD), vitamin A-deficient and ALA-sufficient (VADALAS), or vitamin A- and ALA-deficient (VADALAD) diet. After 7 wk of feeding, liver and colon choline (CPG) and ethanolamine (EPG) phosphoglyceride FA were analyzed. The VADALAS compared with the VASALAS rats had elevated levels of both DHA (P< 0.05) and OA (P < 0.005) in liver CPG and EPG. In contrast, the VADALAD group had a lower DHA (P < 0.01) and higher OA (P < 0.005) level in CPG and EPG of both tissues than their VASALAD counterparts. ALA deficiency reduced DHA and enhariced OA levels in liver and colon CPG and EPG in both the vitamin A-sufficient (VASALAS vs. VASALAD) and -deficient (VADALAS vs. VADALAD) rats (P < 0.005). The study demonstrates that ALA deficiency reduced DHA and enhanced OA levels in tissue membranes, and dietary vitamin A deficiency has a profound effect on membrane DHA and OA in rat tissues. Both vitamin A and DHA are involved in a myriad of vital physiological functions pertaining to growth and development and health. Hence, there is a need for a further study to unravel the mechanism by which vitamin A influences membrane DHA and OA.

Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids

The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause of non-remediable blindness and visual impairment, is not well understood. Nevertheless, increased intraocular pressure, and vascular factors such as ocular blood flow deficits are thought to be risk factors. There is evidence of decreased optic nerve blood velocity and increased red blood cell aggregability in POAG. These factors are influenced by fatty acids. We have investigated if glaucoma patients have abnormal blood fatty acid composition. Patients with POAG ( n = 10 ) and their healthy siblings ( n = 8 ) were enrolled. Compared with their healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA, P < 0.01 ), and docosahexaenoic (DHA, P < 0.05 ) fatty acids and total ω3 long-chain polyunsaturated fatty acids (LCPUFA) ( P < 0.05 ) in red cell choline phosphoglycerides (CPG); decreased EPA ( P < 0.05 ) in ethanolamine phosphoglycerides (EPG); lower EPA ( P < 0.05 ) and total ω3 LCPUFA ( P < 0.05 ) in serine phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total ω3 LCPUFA in plasma CPG ( P < 0.005 ) and triglycerides ( P < 0.05 ) . These findings may be significant, since EPA and DHA could modulate impaired systemic microcirculation and ocular blood flow and optic neuropathy, which are the main physiological changes associated with glaucoma.

Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance

Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Arachidonic Acid Predominates in the Membrane Phosphoglycerides of the Early and Term Human Placenta

The aim of this study was to determine whether the high concentration of arachidonic acid (AA) in term placentae accumulates during pregnancy or is an inherent characteristic of placental lipids. We investigated the lipid content and fatty acid composition of the human placental phospholipids at 2 gestational periods, early in pregnancy (8-14 wk, n = 48) and at term (38-41 wk of gestation, n = 19). The subjects were healthy, normotensive, and free of medical and obstetric complications. The lipid concentration of placentae increased from 0.8% in early gestation to 1.4% at term (P < 0.0001). The mean proportions of AA were lower in the choline (P < 0.05), inositol (P < 0.0001), and ethanolamine (P < 0.0001) phosphoglycerides of the term compared with the early placenta. In contrast, the proportions of the immediate precursor of AA, dihomo-gamma-linolenic acid (DGLA), were higher in the term placenta, particularly in the inositol and serine phosphoglycerides (P < 0.0001). In sphingomyelin, the percentage of lignoceric acid was increased and that of nervonic acid was reduced at term (P < 0.01). The dominance of AA, particularly in the early placenta, suggests that it has an important role for placental development, i.e., organogenesis and vascularization. There was no evidence of an accumulation of AA in the placenta toward term, which might be a trigger for parturition. In contrast, the increased proportion of DGLA (precursor of the vasorelaxant and anticoagulant prostaglandin E(1)) at term is more consistent with a profile favoring optimal blood flow to nourish the fetal growth spurt.

Translocation of Ethanolamine Phosphoglyceride is Required for Initiation of Apoptotic Death in OLN-93 Oligodendroglial Cells

The possible interplay between extracellular signal-regulated protein kinase (ERK) activation and ethanolamine phosphoglycerides (PG) membrane bilayer translocation following oxidative stress (OS) (0.5 mM H2O2/0.05 mM Fe2+), was examined in oligodendroglia, OLN93, cells with altered plasma membrane PG composition. Cells supplemented with 50 microM docosahexaenoic acid (DHA, 22:6n3) to increase the number of potential double bond targets for OS in ethanolamine-PG (EPG) were compared to cells with diminished content of EPG, attained by the addition of 0.5 mM N,N-dimethylethanolamine (dEa). After 30 min OS, EPG translocation accompanied by sustained ERK activation and nuclear translocation culminating in apoptosis was found in DHA-supplemented cells in contrast to no EPG translocation, a brief ERK activation, but no nuclear translocation, and no cell death in DHA/dEa-supplemented cells. DHA/dEa-supplemented cells pretreated with the protein-tyrosine phosphatases inhibitor Na3VO4 followed by OS, although expressing a sustained ERK activation and nuclear translocation, failed to show apoptosis and lacked EPG translocation. In DHA-supplemented cells U0126, a MEK inhibitor, prevented ERK activation and EPG translocation and protected from cell death. These findings most likely indicate that ERK activation is an indispensable component for the signaling cascades leading to EPG translocation but only activation of the latter is leading to OS-induced apoptotic cell death.

Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine

This study was conducted to determine whether dietary ganglioside (GG) increases the content of ether phospholipids (EPL) in intestinal mucosa. Weanling Sprague-Dawley rats were fed a semipurified diet consisting of 20% fat as a control diet. Two experimental diets were formulated by adding either 0.1% (w/w fat) GGs (GG diet) or 1.0% (w/w fat) sphingomyelin (SM diet) to the control diet. Fatty acid methyl esters from the alkenylacyl, alkylacyl and diacyl subclasses of phospholipids were measured to determine total and molecular percentage of EPL comprising the choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG) fraction. Animals fed the GG diet significantly increased total EPL content both in CPG (by 36%) and in EPG (by 66%), and the molecular percentage of EPL in CPG (by 76%) and in EPG (by 59%) compared to animals fed the control diet. Dietary GG-induced increase in EPL resulted in a higher level of polyunsaturated fatty acids (PUFA) specifically in 20:4n-6 and 22:6n-3 compared to control animals, leading to a decrease in the ratio of saturated fatty acids (SFA) to PUFA both in CPG and in EPG. Feeding animals the SM diet showed a higher level of EPL than control animals with a concomitant increase in 22:6n-3 in EPL. The present data demonstrate that dietary GG increases the content and composition of EPL containing PUFA in the weanling rat intestine.