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PubMed1982

[Influence of centrophenoxine on the incorporation of 32P into glycerophosphatides of neurons and gliocytes (author's transl)].

Investigations on the incorporation of intraventricularly injected 32P in neuronal and glial phosphatidylinositol, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine and ethanolamine plasmalogen at intervals ranging from 5 to 60 min showed different incorporation rates of the radioactive precursor into neuronal and glial phosphatides. The incorporation rate of 32P into the different glycerophosphatides was faster in neurons as compared to the gliocyte compartment. Phosphatidylinositol showed the fastest and ethanolamine plasmalogen the slowest incorporation of 32P in both neurons and gliocytes. Centrophenoxine (meclofenoxate, Helfergin) increased the incorporation of 32P into phosphatidylserine and ethanolamine plasmalogen of both glial and neuronal cell bodies whereas the incorporation of the radioactive precursor into phosphatidylcholine was slightly inhibited. The incorporation rate into phosphatidylinositol and phosphatidylethanolamine was not influenced by centrophenoxine. The data obtained in the present work suggest that centrophenoxine may stimulate excitatory neurons and may be involved in the process of synaptic transmission and axonal conduction.

Animals↗
PubMed1977

Plasmalogenase activities in neuronal perikarya, astroglia, and oligodendroglia isolated from bovine brain.

Plasmalogenase (EC 3.3.2.-, 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphorylethanolamine aldehydrogendrolase) activities were assayed with the plasmalogens in dispersed myelin as the substrate. The activities were 6,7-mumoles/mg protein per hr in oligodendroglia from white matter, and 1.1 and 0.6 for astroglia and neuronal perikarya from gray matter. Myelin had no plasmalogenase activity. Thus, both the normal catabolism of myelin plasmalogens and the accelerated hydrolysis of plasmalogens in demyelination is probably carried out by oligodendroglial plasmalogenase.

Animals↗
PubMed1998

Analysis of stable oxidized molecular species of glycerophospholipids following treatment of red blood cell ghosts with t-butylhydroperoxide.

A model of lipid peroxidation was employed to investigate the formation of oxidized phospholipids in red blood cell membranes after treatment with t-butylhydroperoxide (tBuOOH). On-line normal-phase HPLC/mass spectrometry (LC/MS) with electrospray ionization was used to separate phospholipid classes and analyze the distribution of the major poly-unsaturated fatty acyl groups and corresponding oxidation products. Arachidonic acid was observed primarily in plasmalogen glycerophosphoethanolamine (GPE), whereas linoleic acid was equally distributed in 1,2-diacyl-GPE and glycero-phosphocholine (GPC) lipids. The additions of one and two oxygen atoms to poly-unsaturated phospholipid molecular species were observed as the major, stable products after incubation with tBuOOH. Tandem mass spectrometry was utilized to further structurally characterize the oxidized fatty acyl groups which were identified as 5-, 8-, 9-, 11-, 12-, and 15-hydroxy-eicosatetraenoate (HETE) and 5-, 12-, and 15-hydroperoxyeicosatetraenoate (HpETE) in addition to 9- and 13-hydroxyoctadecadienoate (HODE) and 9- and 13-hydroperoxyoctadecadienoate (HpODE). Although 18:0p/20:4-GPE was the predominate phospholipid species containing arachidonic acid, the major species containing HETE and HpETE were the 1,2-diacyl-GPE with hexadecanoate as the sn-1 substituent. This result would be consistent with a differential pathway of oxidative degradation of arachidonoyl plasmalogen GPE suggesting a unique role for this plasmalogen molecular species glycerophospholipid.

Chromatography, High Pressure Liquid↗
PubMed1999

Selective inhibition of phospholipases by atiprimod, a macrophage targeting antiarthritic compound.

Azaspiranes are cationic amphiphilic compounds that are active in a number of models of autoimmune disease and transplantation. Repeated administration of cationic amphiphiles induces phospholipid accumulation in a variety of species. The present study was conducted to explore the mechanism of phospholipid accumulation in rats caused by treatment with the novel azaspirane, SK&F 106615 (atiprimod). Atiprimod inhibited the activities of partially purified phospholipases A(2) and C, but not D, in a noncompetitive manner in vitro. Treatment of rats for 28 days with 10 mg/kg/day of atiprimod increased the contents of arachidonate-containing molecular species within plasmalogen subclasses of hepatic phosphatidylcholine and phosphatidylethanolamine. In contrast, diacyl-linked species were not affected, indicating a selective effect upon an hepatic plasmalogen-selective phospholipase A(2). Taken together, the data suggest that the beneficial effects of atiprimod in autoimmune diseases may involve inhibition of phospholipase A(2) and C activities. Further, the data suggest that atiprimod is a selective inhibitor of plasmalogen-selective phospholipase A(2) in vivo.

Animals↗
PubMed1978

Studies of rat brain choline ethanolamine phosphotransferases using labeled alkylacylglycerol as substrate with evidence for reversibility of the reactions.

Cholinephosphotransferase activity in brain microsomes may be assayed with labeled alkylacylglycerols or with CDP-choline with label in the phosphocholine with nearly identical results. The direct linear plot method was used for evaluation of Michaelis-Menten kinetic parameters. Most of the cholinephosphotransferase activity is in microsomes and a stimulatory factor seems to be present in the cytosol. Incubation of microsomes with labeled alkylacylglycerols and CDP-choline, in the initial absence of CDP-ethanolamine, produced labeled ethanolamine glycerophospholipids as well as labeled choline glycerophospholipids. Since the labeling of ethanolamine glycerophospholipids was increased by the addition of CMP, the labeling was probably due to the reversal of ethanolamine phosphotransferase to yield CDP-ethanolamine produced by the choline phosphotransferase reaction. Cholinephosphotransferase was reversed more readily than ethanolaminephosphotransferase in brain as it is in liver (Kanok and Ohno, 1973). Only trace quantities of plasmalogens were formed with labeled alkylacylglycerols. Previous results of plasmalogen labeling from labeled CDP-nucleotides were apparently due to reversal of phosphotransferase reactions. Alkylacylglycerophospholipids are not good substrates for plasmalogen formation, even when they are incorporated into microsomes.

Animals↗
PubMed1996

The modulation of choline phosphoglyceride metabolism in human colon cancer.

Colorectal cancer has a high incidence of morbidity and mortality in the North American population. Elevated levels of plasmalogens have been reported in some neoplastic tissues including colon tumors, but the mechanism for this increase has not been defined. Since changes in plasmalogen level are usually associated with changes in the other phospholipid subclasses, a general increase in all phospholipid subclasses may also be found in colonic neoplasms. In this study, the levels of the major phospholipids, including their plasmalogen and diacylphospholipid subclasses, were found to be elevated in human malignant colonic tissues. Since phosphatidylcholine is the most prominent type of phospholipid found in both malignant and control tissues, the mechanism for its accumulation during malignancy was investigated. Decreases in phospholipase C and D activities were observed in tumor samples, but an enhancement of the CTP: phosphocholine cytidylyltransferase activity was also detected. Immunoblotting analysis revealed that the elevated cytidylyltransferase activity was caused by a three-fold increase in the level of enzyme protein during tumor development. Based on these enzyme studies, we conclude that the high level of phosphatidylcholine in colon tumors resulted from a decrease in its turnover and an increase in its expression.

Colon↗
PubMed1980

Incorporation of linoleic acid into membrane glycerophospholipids from rat brain submitted to ischemia and hypoxia.

In the presence of ATP, Mg and CoA-SH]1-14C]linoleic acid was incorporated into membrane phospholipids (P2 fraction and synaptosomes) prepared from rat brain cortex. The relative order for linoleate incorporation was: phosphatidyl-choline greater than phosphatidylethanolamine greater than phosphatidylinositol greater than ethanolamine plasmalogen greater than phosphatidylserine. The incorporation of labeled linoleate into P2 fraction phospholipids was investigated in rats, aged 4, 16, and 90 days, after being subjected to ischemic and hypoxic conditions. With the exception of a small increase in the incorporation of the radioactivity into diacyl-GPC, little change in incorporation profile was observed with 4-day-old rats submitted to ischemic and hypoxic conditions. However, the incorporation of labeled linoleate into membrane phospholipids was decreased in 16- and 90-day-old rats being subjected to ischemic and hypoxic conditions. Among the phospholipids, the decrease in incorporation of radioactivity was most prominent with ethanolamine plasmalogens and phosphatidylinositol, although the radioactivity of phosphatidylcholine seemed to remain relative constant. The decreased incorporation activity in these two age groups was noted along with concomitant increase in the FFA content, whereas in FFA was not observed in the 4-day-old brain samples. Thus, the specific decrease in labeling of ethanolamine plasmalogens and phosphatidylinositol may be the result of increased enzymic degradation of these compounds after ischemic and hypoxic treatment. Furthermore, the decrease in incorporation of linoleate into membrane phospholipids may be due to an increase in the membrane FFA pool which subsequently gave a dilution of the labeled precursor.

Animals↗
PubMed1994

Meningioma phospholipid profiles measured by 31P nuclear magnetic resonance spectroscopy.

Fourteen cases of intracranial meningioma were characterized after chloroform/methanol extraction by 31P nuclear magnetic resonance (NMR) spectroscopy at 202.4 MHz. Each phospholipid class detected in the extracts was identified and quantitated in terms of its molar percentage relative to the total phospholipids measured. The following phospholipids were assayed by 31P NMR: phosphatidylglycerol, phosphatidic acid, diphosphatidylglycerol, ethanolamine plasmalogen, phosphatidylethanolamine (PE), lysophosphatidylinositol, phosphatidylserine, sphingomyelin, lysophosphatidylcholine (LPC), phosphatidylinositol (PI), sphingosylphosphorylcholine and phosphatidylcholine. In addition, two unidentified phospholipids were detected with resonances at 0.13 and -0.78 ppm, respectively. Three distinct types of spectra were obtained on the extracts and grouped accordingly for comparison purposes. Type 1 tumors showed unusual 31P NMR profiles with low levels of PE and PI and elevated levels of LPC; type 2 tumors were characterized by low levels of the ethanolamine phospholipids and near equivalent levels of PI and LPC. The spectra of type 1 and type 2 tumors were characteristic of degenerative cells that lacked membrane permeability associated with loss of ethanolamine plasmalogen in the presence of significant phospholipid turnover. Meningiomas belonging to the third spectral type showed characteristics similar to those of normal tissues with normal levels of PE and ethanolamine plasmalogen, as well as very low levels of LPC relative to PI. Type 3 tumors lacked the characteristic signs of degeneration noted in type 1 and type 2 tumors. The data corroborate and augment in vivo spectroscopic findings reported earlier and demonstrate the value of 31P NMR spectroscopic phospholipid analysis on lipid extracts for the characterization of meningiomas.

Humans↗
PubMed1996

Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis.

A patient with classic Zellweger syndrome was treated with docosahexaenoic acid ethyl ester (DHA-EE) for three months. Five other patients with Zellweger variants (four of them less than one-year-old and a five-year-old) were treated with DHA-EE until normalization of the DHA levels in erythrocytes. When arachidonic acid (AA) concentration decreased, AA was added to the diet. Thereafter, a combined treatment with DHA plus AA followed, in a variable proportion that allowed the high levels of DHA in erythrocytes to be maintained. In the patient with Zellweger syndrome, DHA therapy produced an increase in plasmalogen and a decrease in 26:0 and 26:1. No clear clinical improvement could be detected in this patient during the short period of treatment with DHA-EE. The most consistent clinical effect produced by DHA therapy in the other patients with disorders of peroxisomal biogenesis was visual improvement, even in those patients that were virtually blind before the treatment. In general, the developmental curve began to accelerate. The infants became more alert, acquired better visual and social contact and muscular tone improved, with the beginning of good head control. The liver tests tended to normalize and some patients showed a reduction of hepatomegaly. All these favorable changes occurred when the patients were taking the DHA-EE alone. In some of the patients, muscular tone seemed to improve further after introducing AA supplements. From the biochemical point of view, the plasmalogen levels increased in most cases in erythrocytes, and the two ratios 26:0/22:0 and 26:1/22:0 decreased in plasma. In some patients there was a tendency for 26:1 to increase in plasma and for 18:0 plasmalogen to decrease in erythrocytes when AA was introduced in the diet. The significance of these findings remains to be elucidated, but they stress the importance of strict monitoring and control of the polyunsaturated fatty acids status during DHA therapy.

Docosahexaenoic Acids↗
PubMed1988

Selective hydrolysis of ether-containing glycerophospholipids by phospholipase A2 in rabbit lung.

The role of phospholipase A2 (PLA2) in the simultaneous generation of lyso-platelet-activating factor and arachidonic acid was investigated by examining the calcium dependency and substrate specificity of PLA2 activities in rabbit lung microsomes. Alkylarachidonoylglycerophosphocholine (alkylarachidonoyl-GPC) was preferentially hydrolyzed as compared to acylarachidonoyl-GPC, and both arachidonate-containing substrates were cleaved to a greater extent as compared to alkyl- and acyl-substrates with oleate at the sn-2 position. Hydrolysis of alkylacyl-GPC substrates was not dependent on calcium in the presence of EGTA (1 mM); however, addition of calcium (2 mM) increased hydrolysis of acylarachidonoyl-GPC 2-fold and hydrolysis of acyloleoyl-GPC 10-fold. Substitution of an alkenyl group in the sn-1 position further enhanced calcium-independent PLA2 hydrolysis, and another substitution of arachidonic acid at the sn-2 position of the plasmalogen substrates substantially increased hydrolysis as compared to hydrolysis of substrates containing oleic acid. Hydrolysis of the choline plasmalogen was 3-fold greater than hydrolysis of the ethanolamine plasmalogen containing arachidonate. Preferential calcium-independent hydrolysis of alkylacyl-GPC substrates was observed in several tissues, including adult and fetal rabbit lung and adult rabbit kidney and human amnion. PLA2 substrate specificity may account for the preferential hydrolysis of arachidonoyl-containing alkyl-GPC in several cell types and explain the simultaneous generation of the precursors of two potent autacoids, platelet-activating factor and eicosanoids.

Aging↗
PubMedDate not supplied

Effective lovastatin therapy in elderly hypercholesterolemic patients - an antioxidative impact?

The effect of 3 months lovastatin therapy on serum lipids, apolipoproteins, alpha-tocopherol and red cell membrane fatty acid pattern was assessed in twelve elderly ambulatory patients (mean age 70.9+/-8.0 years) with hypercholesterolemia type IIa according to Fredrickson. After a run-in period of 4 weeks without drug therapy, the patients were given a daily dose of 20 mg lovastatin. The treatment resulted in statistically significant decreases in mean serum low density lipoprotein cholesterol (LDL-CH, -34%), in the atherogenic index LDL-CH/HDL-CH (-35%) and in the concentration of apolipoprotein B (-26%). No change in the vitamin E status, as related to plasma total lipids, was observed during the 3 months of therapy. The fatty acid pattern of phospholipids from red cell membranes showed an increase in linoleic acid metabolites and a decrease in the precursor linoleic acid, indicating an induction of fatty acid desaturases by lovastatin. In addition, an increase in the plasmalogen portion of erythrocyte membrane phospholipids was exhibited by increases in the proportion of fatty aldehyde dimethyl acetals (DMA) in the fatty acid pattern. The plasmalogens increase may counteract the slow but consistent decrease in their concentration in red cell membranes and human aortas with increasing donor age and in arteriosclerosis. Since plasmalogens may function as physiological antioxidants, the observed increase in DMA concentration might reflect a previously unrecognized antioxidative principle of a lovastatin therapy.

Journal Article↗
PubMed2000

Peroxidation of arachidonate containing plasmenyl glycerophosphocholine: facile oxidation of esterified arachidonate at carbon-5.

Oxidation of 1-O-hexadec-1'-enyl-arachidonoyl glycerophosphocholine (16:0p/20:4-GPC) by hydroxyl radical generated from Cu(II)/H(2)O(2) was found to yield major products corresponding to free carboxylic acids of 5-hydroxyeicosatetraenoic acid and several 5, 12-dihydroxyeicosatetraenoic acid. These products were characterized by electrospray tandem mass spectrometry based upon characteristic product ion spectra, as well as HPLC retention time. Several products were found to be biologically active in terms of elevating neutrophil intracellular calcium ion concentration. When mixed micelles of 16:0p/20:4-GPC were treated with Cu(II)/H(2)O(2), oxidation of the arachidonate esterified to the plasmalogen glycerophosphocholine lipid resulted in the most abundant products oxidized at carbon-5 of esterified arachidonate, but free carboxylic acid products were not formed. The mechanism of formation of these oxidized products is suggested to involve a cooperation between the sn-1 vinyl ether substituent and the arachidonoyl substituent at sn-2 of the glycerophospholipid to direct oxidation of the arachidonate ester at carbon-5. Since arachidonic acid is found in high abundance within most plasmalogen glycerophospholipids, the susceptibility of plasmalogens to free radical oxidation likely involves concomitant oxidation of the arachidonyl radyl group esterified at the sn-2 position.

Arachidonic Acid↗
PubMed2001

Endothelial cell PAF synthesis following thrombin stimulation utilizes Ca(2+)-independent phospholipase A(2).

Platelet activating factor (PAF) is a potent lipid autocoid that is rapidly synthesized and presented on the surface of endothelial cells following thrombin stimulation. PAF production may occur via de novo synthesis or by the combined direct action of phospholipase A(2) (PLA(2)) and acetyl-CoA:lyso-PAF acetyltransferase or via the remodeling pathway. This study was undertaken to define the role of PLA(2) and plasmalogen phospholipid hydrolysis in PAF synthesis in thrombin-treated human umbilical artery endothelial cells (HUAEC). Basal PLA(2) activity in HUAEC was primarily found to be Ca(2+)-independent (iPLA(2)), membrane-associated, and selective for arachidonylated plasmenylcholine substrate. Thrombin stimulation of HUAEC resulted in a preferential 3-fold increase in membrane-associated iPLA(2) activity utilizing plasmenylcholine substrates with a minimal increase in activity with alkylacyl glycerophospholipids. No change in cystolic iPLA(2) activity in thrombin-stimulated HUAEC was observed. The thrombin-stimulated activation of iPLA(2) and associated hydrolysis of plasmalogen phospholipids was accompanied by increased levels of arachidonic acid (from 1.1 +/- 0.1 to 2.8 +/- 0.1%) and prostacyclin release (from 38 +/- 12 to 512 +/- 24%) as well as an increased level of production of lysoplasmenylcholine (from 0.6 +/- 0.1 to 2.1 +/- 0.3 nmol/mg of protein), lysophosphatidylcholine (from 0.3 +/- 0.1 to 0.6 +/- 0.1 nmol/mg of protein), and PAF (from 790 +/- 108 to 3380 +/- 306 dpm). Inhibition of iPLA(2) with bromoenol lactone resulted in inhibition of iPLA(2) activity, plasmalogen phospholipid hydrolysis, production of choline lysophospholipids, and PAF synthesis. These data indicate that PAF production requires iPLA(2) activation in thrombin-stimulated HUAEC and may occur through the CoA-independent transacylase remodeling pathway rather than as a direct result of the PLA(2)-catalyzed hydrolysis of membrane alkylacyl glycerophosphocholine.

Chromatography, High Pressure Liquid↗
PubMed2000

Peroxisome distribution along the crypt-villus axis of the guinea pig small intestine.

Peroxisomes and peroxisomal enzyme expression were investigated biochemically and morphometrically in guinea pig intestinal epithelial cells at different stages of their migration along the crypt-villus axis. Epithelial cells were sequentially isolated along the axis and the specific activities of the peroxisomal enzymes catalase and acyl-CoA oxidase were found to be significantly higher in differentiated and mature cells situated at the villus tip and stem than in the crypt. Conversely, 1-alk-1'enyl, 2-acyl phospholipid (plasmalogen) concentration in the crypt and middle villus was significantly higher than in villus tip cells. Assay of alkyl DHAP synthase and fatty acyl CoA reductase (enzymes responsible for the production of plasmalogen precursors) showed no correlating activity gradient with plasmalogen concentration. Morphometric analysis revealed that peroxisomes were present even in the most immature stem cells, however, their number and volume and surface densities increased as the epithelial cell developed as did the proportion of elongated and vermiform peroxisomes to spherical structures. Senescent cells at the tip of the villus, however, showed a dramatic decrease in number of peroxisomes per cell possibly due to cellular degradation. We conclude that the peroxisomal compartment of the guinea pig small intestinal epithelial cell develops as a function of cell development possibly reflecting adaptation to maximise its metabolic capacity.

Animals↗
PubMed1967

Lipid composition and metabolism in testicular and ejaculated ram spermatozoa.

1. Spermatozoa collected directly from the testis of the conscious ram contain 25% more phospholipid than ejaculated spermatozoa. The concentration of lecithin, phosphatidylethanolamine and ethanolamine plasmalogen was greater in testicular spermatozoa; little difference was observed in choline plasmalogen. Both types of spermatozoa had significant amounts of cardiolipin and alkyl ether phospholipid. 2. The fatty acids in the phospholipid extracted from testicular spermatozoa have a very high content of palmitic acid. The phospholipids of ejaculated spermatozoa contained less palmitic acid, but more myristic acid. 3. Ejaculated spermatozoa contained less acyl ester and cholesterol. It is suggested that lipids are a source of substrate for spermatozoa during their passage through the epididymis. 4. Testicular spermatozoa when incubated with [U-(14)C]glucose incorporated more radioactivity into the glycerol part of the phospholipid and neutral lipid fractions than did ejaculated cells. The distribution of radioactivity in the individual phospholipids and neutral lipids was similar for both cell types. No radioactivity was detected in choline plasmalogen, which accounted for approx. 40% of the total phospholipid. 5. Testicular spermatozoa incorporated more radioactivity from glucose into formate than into acetate, whereas a higher proportion of radioactivity was found in acetate in ejaculated cells. 6. The implications of these lipid changes in the process of spermatozoal maturation are discussed.

Animals↗
PubMed1998

Development of pulmonary lipophilic antioxidants and peroxidizable lipids during lung maturation.

The objective of this article is to test whether the concentration of potentially oxidizable lipids (polyunsaturated fatty acids [PUFA], total and free cholesterol) and lipophilic antioxidants (plasmalogens, vitamin E) in the fetal lung correlate with lung maturation (P/S ratio). In amniotic fluid palmitic/stearic acid (P/S) ratio, concentrations of PUFA, total and free cholesterol, vitamin E, and plasmalogens were measured. Ratio of PUFA to stearic acid (PUFA/S ratio) was determined in lung effluent of 15 preterm infants with IRDS and compared with values from 15 term healthy infants. Concentrations of plasmalogens, PUFA, total and free cholesterol increase significantly with increasing P/S ratio. No correlation of vitamin E with lung maturation has been found. The PUFA/S ratio is significantly lower in lung effluent of preterm (0.79 +/- 0.27) when compared with term infants (2.02 +/- 0.38). Our results suggest that the higher susceptibility of preterm infants for oxidative lung injury is not caused by an unfavorable ratio of oxidizable lipids to lipophilic antioxidants in surfactant, but rather by a lower amount of PUFA containing surfactant lipids. Our results are in accordance with data from Sosenko et al. who have shown that high levels of PUFA in the rat lung have a protective effect against oxygen-induced lung damage.

Amniotic Fluid↗
PubMed1982

Lysoplasmalogenase--a microsomal enzyme from rat brain.

An enzymic activity of rat brain that liberates radioactive free aldehydes from 1-[1-14C]alk-1'-enyl-sn-glycero-3-phosphoethanolamine (lyso-plasmalogen) is described. It was present mainly in microsomal fractions (crude) of brains of rats of different ages. The highest specific enzyme activity was found in 21-day-old animals. The formation of free aldehyde was dependent on the amount of enzyme protein as well as the amount of substrate added, and was linear to the incubation time up to 60 min. The pH optimum was between 7.1 and 7.3. Bivalent cations (Mg2+, Ca2+) and detergents inhibited the reaction. However, the same cell fractions as well as extracts of acetone-dried powder of brain from young or old rats possessed no enzyme activity for liberating the aldehyde from the acylated substrates: 1-[1-14C]alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmalogen) or plasmalogen of ox corpus callosum.

Aging↗
PubMed1993

Basis for phospholipid incorporation into peripheral nerve myelin.

To characterize the mechanism(s) for targeting of phospholipids to peripheral nerve myelin, we examined the kinetics of incorporation of tritiated choline-, glycerol-, and ethanolamine-labeled phospholipids into four subfractions: microsomes, mitochondria, myelin-like material, and purified myelin at 1, 6, and 24 h after precursors were injected into sciatic nerves of 23-24-day-old rats. As validation of the fractionation scheme, a lag (> 1 h) in the accumulation of labeled phospholipids in the myelin-containing subfractions was found. This lag signifies the time between synthesis on organelles in Schwann cell cytoplasm and transport to myelin. In the present study, we find that sphingomyelin (choline-labeled) accumulated in myelin-rich subfractions only at 6 and 24 h, whereas phosphatidylserine (glycerol-labeled) and plasmalogen (ethanolamine-labeled) accumulated in the myelin-rich fractions by 1 h. The later phospholipids accumulate preferentially in the myelin-like fraction. These results are consistent with the notion that the targeting of sphingomyelin, a lipid present in the outer myelin leaflet, is different from the targeting of phosphatidylserine and ethanolamine plasmalogen, lipids in the inner leaflet. These findings are discussed in light of the possibility that sphingomyelin targeting is Golgi apparatus based, whereas phosphatidylserine and ethanolamine plasmalogen use a more direct transport system. Furthermore, the routes of phospholipid targeting mimic routes taken by myelin proteins P0 (Golgi) and myelin basic proteins (more direct).

Animals↗