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PubMed1980

Alterations of lipid and protein composition in myelin of acute experimental allergic neuritis.

Lipid and protein components of the myelin isolated from the spinal roots of rabbits at the acute stage of experimental allergic neuritis (EAN) and of control rabbits were analyzed. The results obtained from the EAN myelin in comparison with the control myelin were as follows: (1) The content of cholesterol increased and that of cerebroside significantly decreased, while the content of plasmalogen and phospholipid was not changed. The level of cholesterol ester was negligible both in EAN and control myelin. (2) The sum of saturated fatty acids increased while the sum of unsaturated fatty acids decreased. (3) The decrease of the basic proteins P1 and P2 was more noticeable than that of the PO + Y protein. Concomitant to these observations, with 1,6-diphenyl 1,3,5-hexatriene as a fluorescent probe, the microviscosity of the isolated myelin was measured. The results indicated that myelin obtained from EAN was less fluid. Diminished myelin fluidity in EAN was consistent with the results of the lipid and fatty acid analyses.

Acute Disease↗
PubMed1989

Time course for labeling of brain membrane phosphoinositides and other phospholipids after intracerebral injection of [32P]-ATP. Evaluation by an improved HPTLC procedure.

An improved two-dimensional HPTLC procedure was developed for separating phospholipids including individual phosphoinositides, phosphatidic acids and plasmalogens. This procedure was used to examine the time course for uptake of label by phospholipids in brain subcellular membranes after intracerebral injection of [gamma-32P]-ATP. There were considerable differences in the phospholipid labeling pattern among different subcellular fractions. In particular, a high proportion of labeled phosphatidylinositol 4,5-bisphosphates and phosphatidic acids was found in the myelin fraction during the initial 4 hr after injection. In other subcellular fractions, labeling of phosphoinositides was maximum at 2 hr, but with prolonged time, poly-phosphoinositides started to show a decline in radioactivity whereas labeling of other phospholipids continued to show a steady increase instead. Results indicate at least two different modes for the uptake of label by brain membrane phospholipids after intracerebral injection of [32P]-ATP.

Adenosine Triphosphate↗
PubMed1993

Effect of stobadine on lipid peroxidation and phospholipids in rabbit spinal cord after ischaemia.

Stobadine, a drug with the pyridoindol structure, was compared with thiopental and pentobarbital for its ability to inhibit stimulated peroxidation in homogenates of spinal cord in vitro. The antioxidative capacity of the drug exceeded that of barbiturates more than 100-fold. Stobadine was also shown to inhibit the increase in formation of TBA-RS in homogenates of rabbit spinal cord, subjected to 20 min ischaemia, to the level comparable with controls. Administration of the drug (6 mg kg-1) to animals 5 min before 20 min ischaemia had no effect on level of lipid peroxidation products in the spinal cord; however, it slowed down stimulated Fe(2+)-dependent peroxidation after in vitro incubation of the homogenates and increased the concentration of phosphatidylserine and ethanolamine plasmalogens, as compared with non-treated animals. Application of stobadine 2 min before the release of an aortic occlusion increased the antiradical capacity in homogenates of spinal cord and revealed an ameliorating effect on the composition of phospholipids.

Animals↗
PubMed1985

Ether-phospholipid composition in neutrophils and platelets.

It is well documented that ether-lipids, especially the 1-0-alkyl-2-0-acyl-sn-glycero-3-phosphocholine, can serve as precursors in paf-acether (platelet-activating factor) biosynthesis. This study was undertaken to determine the amount of these compounds in two cell types which are good producers of paf-acether: human neutrophils and rabbit platelets. The method of phospholipid analysis was based on selective destruction of diacyl molecules by lipase from guinea pig pancreas and of plasmalogens by acidolysis; phospholipids were then separated by bidimensional thin-layer chromatography. In platelets as in neutrophils, the major phospholipids were choline (37%) and ethanolamine (30 and 32%, respectively) phosphoglycerides and sphingomyelin (18 and 16%, respectively). In rabbit platelets the 1-alkyl molecules represented 15% of the choline class (0.7 nmol/10(7) cells). Neutrophils differed strikingly from platelets by the high level of these molecules which constituted 50% of the choline class (16.3 nmol/10(7) cells). It therefore appears that in the two cell types, the amount of 1-0-alkyl-2-0-acyl-sn-glycero-3-phosphocholine largely exceeded that would be necessary for paf-acether biosynthesis.

Animals↗
PubMed1985

Lipids of nervous tissue: composition and metabolism.

As indicated in the Introduction, the many significant developments in the recent past in our knowledge of the lipids of the nervous system have been collated in this article. That there is a sustained interest in this field is evident from the rather long bibliography which is itself selective. Obviously, it is not possible to summarize a review in which the chemistry, distribution and metabolism of a great variety of lipids have been discussed. However, from the progress of research, some general conclusions may be drawn. The period of discovery of new lipids in the nervous system appears to be over. All the major lipid components have been discovered and a great deal is now known about their structure and metabolism. Analytical data on the lipid composition of the CNS are available for a number of species and such data on the major areas of the brain are also at hand but information on the various subregions is meagre. Such investigations may yet provide clues to the role of lipids in brain function. Compared to CNS, information on PNS is less adequate. Further research on PNS would be worthwhile as it is amenable for experimental manipulation and complex mechanisms such as myelination can be investigated in this tissue. There are reports correlating lipid constituents with the increased complexity in the organization of the nervous system during evolution. This line of investigation may prove useful. The basic aim of research on the lipids of the nervous tissue is to unravel their functional significance. Most of the hydrophobic moieties of the nervous tissue lipids are comprised of very long chain, highly unsaturated and in some cases hydroxylated residues, and recent studies have shown that each lipid class contains characteristic molecular species. Their contribution to the properties of neural membranes such as excitability remains to be elucidated. Similarly, a large proportion of the phospholipid molecules in the myelin membrane are ethanolamine plasmalogens and their importance in this membrane is not known. It is firmly established that phosphatidylinositol and possibly polyphosphoinositides are involved with events at the synapse during impulse propagation, but their precise role in molecular terms is not clear. Gangliosides, with their structural complexity and amphipathic nature, have been implicated in a number of biological events which include cellular recognition and acting as adjuncts at receptor sites. More recently, growth promoting and neuritogenic functions have been ascribed to gangliosides. These interesting properties of gangliosides wIll undoubtedly attract greater attention in the future.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Metabolism of dietary genotoxins by the human colonic microflora; the fecapentaenes and heterocyclic amines.

The microflora of the human colon is a complex ecosystem of anaerobic bacteria which have the capability of enzymatically transforming a variety of dietary (or biliary) compounds to genotoxic metabolites. In the past, most investigators studying the interplay between diet and colonic flora and its role in the etiology of cancers focused on the reductive and glycosidic potential of the bacterial enzymes--many of which reverse the oxidative and conjugative reactions performed by the liver. Recent work in our laboratory has focused on the metabolism of two relatively new classes of genotoxins, the fecapentaenes and the heterocyclic amines (pyrolysis carcinogens). The fecapentaenes (conjugated ether lipids) are produced in the colon by Bacteroides spp. from polyunsaturated ether phospholipids (plasmalogens) whose natural origin and function are unknown. The fecapentaenes are potent direct-acting genotoxins that are detected in the feces of most individuals on normal western diets. The heterocyclic amines, which originate from fried or broiled proteinaceous foods, normally require activation by the liver before being potent mutagens or carcinogens. However, the "IQ" subclass (e.g. IQ and MeIQ) can be activated in the colon by Eubacterium and Clostridium species to a 7-hydroxy form which is directly mutagenic in Salmonella. Although there is no direct evidence that the fecapentaenes or the 7-hydroxy "IQ" compounds influence risk for colon cancer, the potency and prevalence of these bacterial metabolites is cause for concern.

Amines↗
PubMed1985

Studies on the enzymatic pathways of calcium ionophore-induced phospholipid degradation and arachidonic acid mobilization in peritoneal macrophages.

Exposure of mouse peritoneal macrophages to ionophore A23187 caused a rapid and extensive Ca2+-dependent phospholipid degradation and mobilization of arachidonic acid. Phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine all contributed to the arachidonic acid release, although the ethanolamine phospholipids incorporated [3H]arachidonic acid more slowly during the prelabeling period, particularly the plasmalogen form. Several enzymatic pathways could be positively identified as contributing to the ionophore-induced phospholipid degradation by the use of several different radiolabeled phospholipid precursors: (i) a phospholipase A-mediated deacylation, (ii) a phosphodiesterase (phospholipase C) reaction, rapidly generating diacylglycerol units from inositol phospholipids, and (iii) enzymatic processes generating diacylglycerol and CDP- and phosphocholine/ethanolamine from phosphatidylcholine/ethanolamine. The diacylglycerol formed was in part phosphorylated and in part hydrolyzed to monoacylglycerol, with retention of its arachidonic acid. These, and other, results indicate that the Ca2+-ionophore activates several apparently distinct phospholipid-degrading processes, in contrast to stimuli acting via cellular receptors.

Animals↗
PubMed1990

Characterization of lipid composition in stimulated human lymphocytes by 1H-NMR.

Recent in vivo NMR studies have raised interest in the structural changes of cellular lipids during proliferative activity. We investigated the changes in plasma membrane lipid and total cell lipid during mitogenically-stimulated proliferation of human peripheral blood lymphocytes by extraction of lipids and assay by 500 MHz 1H-NMR. Resonances were assigned using one- and two-dimensional spectroscopic techniques, and signals unique to certain species of lipid were identified. Choline and ethanolamine-containing lipids, glycerophospholipid backbones, sphingolipids, cholesterol, plasmalogens and triacylglycerols were readily detected. Resolution of a number of lipid species was not possible, despite the use of high-resolution techniques. NMR values for proliferation-induced changes in the most easily determined parameters, namely the total cholesterol to total phospholipid molar ratio, and phosphatidylcholine, phosphatidylethanolamine and sphingolipid composition, were found to agree with traditional methods. Differences in phospholipid and fatty acid profiles were found between plasma membranes and total cell lipid for resting values and for response to mitogen.

Cell Membrane↗
PubMedDate not supplied

A comparative-evolutionary study of lipids in the aging brain of mice.

The lipids of aging brain were studied using a comparative-evolutionary model involving two species of mice, Mus Musculus (Mus) and Peromyscus leucopus (Peromyscus). Mus ages 2.5 times faster than does Peromyscus. Brain weight, water content, cholesterol, and ethanolamine plasmalogen decreased and phosphatidyl ethanolamine increased in both species with age. Differences between species included 12% more cholesterol/g total lipid extract in Peromyscus than in Mus throughout life, a linear increase with age in lipid phosphorus/g fresh weight at a faster rate in Peromyscus over Mus, and a linear increase in the total lipid extract weight throughout life in Mus but a decrease in Peromyscus. Cerebroside, sulfatide and GM1 ganglioside all increased during maturation and then decreased in old age in both mice. Lipid-bound sialic acid (ganglioside) increased linearly throughout life in Peromyscus but decreased slightly in Mus. These changes are interpreted to mean that the cellular membranes of Peromyscus may be inherently more stable than those of Mus, Peromyscus is better able to preserve its neuronal cell population with age than is Mus, proliferation of non-myelin membranes may occur in both species in advanced age, and both species of mice may experience some loss of myelin with age.

Aging↗
PubMed1994

Inhibition of H2O2 production by iodoaldehydes in cultured dog thyroid cells.

2-Iodohexadecanal (IHDA) has been identified as a major thyroid iodolipid which can be formed upon addition of iodine to the vinyl ether group of plasmalogens (Pereira et al., 1990). In order to test whether IHDA plays a role in the thyroid autoregulation by iodide, we have investigated its effects on the production of H2O2 by cultured dog thyroid cells. IHDA inhibited the formation of H2O2 in dog thyroid cells stimulated by carbamylcholine (CCHOL). In the presence of BSA, which potentiated its action, the effect of IHDA was maximal after 2 h and had an IC50 around 5 microM. The effect of IHDA was not decreased by methimazole, which abolished the inhibition by iodide. IHDA also inhibited the stimulatory effect of bradykinin, but had only a marginal effect on the production of H2O2 induced by ionomycin or phorbol 12-myristate 13-acetate (PMA). The accumulation of inositol phosphates in CCHOL-stimulated thyroid cells was decreased by IHDA. As evaluated by measurements of 51Cr release and [3H]thymidine incorporation into DNA, IHDA had no adverse effect on thyroid cell viability. Several analogs of IHDA, of which the synthesis is described, have been tested for their inhibitory activity. This allowed the identification of two major structural features required for the biological activity: the carbonyl group at C1 and an halogen atom at C2, with iodine conferring a greater activity than bromine, while chlorine and fluorine were inactive. In conclusion, IHDA inhibits the production of H2O2 in CCHOL-stimulated dog thyroid cells by decreasing the phospholipase C cascade activity. This effect involves both the aldehyde function and the iodine atom. These results suggest that IHDA might be the mediator of some of the regulatory actions of iodide on the thyroid gland.

Aldehydes↗
PubMed1994

Inhibition of human thyroid adenylyl cyclase by 2-iodoaldehydes.

2-Iodohexadecanal (IHDA), which can be formed upon addition of iodine to the vinyl ether group of plasmalogens, has been identified as a major thyroid iodolipid (Pereira et al. (1990) J. Biol. Chem. 265, 17018-17025). In this study, we have investigated the possibility that it would be a mediator of the inhibitory effect of iodide on thyroid adenylyl cyclase. In human thyroid membranes, IHDA inhibited the adenylyl cyclase activity stimulated by thyrotropin (TSH), GTP-gamma-S or forskolin (FSK), whereas it did not decrease the specific binding of TSH to its receptors. The inhibitory effect on the cyclase reached a maximum after a 1-h-pre-incubation of the membranes with IHDA at 30 degrees C and was poorly reversible. It was also observed following a 4-h incubation with IHDA at 4 degrees C, a condition in which adenylyl cyclase is protected against heat inactivation. IHDA decreased the Vmax of adenylyl cyclase, but had no effect on the Km for ATPMg2-.IHDA also inhibited the FSK-stimulated adenylyl cyclase activity in liver and kidney cortex membranes, but had no effect on the Mg(2+)-ATPase activity of thyroid membranes. The inhibitory effect of IHDA has also been demonstrated in intact cells. As in membranes, IHDA decreased the rise in cAMP induced by TSH in cultured dog thyroid cells and this inhibition was maintained following pretreatment of the cells with pertussis toxin. In order to evaluate the specificity of the IHDA action, various analogs have been synthesized. This study has permitted the identification of two major structural features required for the inhibition of human thyroid adenylyl cyclase; the terminal aldehyde function and an iodine atom at C2, other halogens being ineffective. In conclusion, we have shown that IHDA exerts a direct inhibitory effect at or near adenylyl cyclase; all the properties of this effect characterized so far are identical to those of the adenylyl cyclase inhibition obtained following the exposure of thyroid tissue to iodide.

Adenylyl Cyclase Inhibitors↗
PubMed1983

Lipid composition of the spinal cord in the fruit bat Rousettus aegyptiacus.

Spinal cords were removed from ten Egyptian fruit bats Rousettus aegyptiacus and the lipids analysed. The major phosphatides were choline glycerophosphatide (32.3%), ethanolamine glycerophosphatide (29.3%), serine glycerophosphatide (15.2%) and phosphatidylinositol (8.4%). Sphingomyelin accounted for 13.8% of the phospholipid. Glycosphingolipids amounted to 43.2 mol/100 mol lipid phosphorus, plasmalogens 32.5 mol/100 mol P and cholesterol 159.5 mol/100 mol P. The fatty acid composition of whole cord, sphingomyelin and non-hydroxy cerebroside were determined. The results were compared with data from other species.

Animals↗
PubMed1984

Lipid composition of brain myelin from normal and hyperphenylalaninemic chick embryos.

The influence of hyperphenylalaninemia on the lipid composition of brain myelin has been investigated in 19-day-old chick embryos. CNP-ase activity was used as myelin marker enzyme for myelin isolation. CNP-ase activity was significantly lower in hyperphenylalaninemic myelin when compared with control. No significant differences were observed after experimental treatment in the total lipid content of myelin as well as in the proportion of cholesterol:phospholipid:galactolipid. Nevertheless, a clear increase in the percentage of esterified cholesterol was found. No appreciable alterations were observed in the phospholipid composition of brain myelin from both control and hyperphenylalaninemic chick embryos. However, the ratio of unsaturated to saturated fatty acids in serine plasmalogen and sphingomyelin was considerably increased by this treatment. This ratio in choline and ethanolamine phosphatides from treated embryos did not differ from that of controls.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1992

Comparative investigation of phospholipids and fatty acids of freshwater molluscs from the Volga river basin.

1. Four Gastropoda species and two Bivalvia species from the Volga river basin were examined. 2. Distribution of phospholipids in the molluscs was studied by qualitative and quantitative micro thin-layer chromatography. 3. Major phospholipid classes, phosphatidylethanolamine and phosphatidylcholine, were found to contain plasmalogens. 4. One mollusc species notably contained 67 fatty acids including 25 saturated (both iso and anteiso), 24 monoenoic, five dienoic, four trienoic and eight polyenoic compounds identified by capillary gas chromatography; fatty acid contents in the other studied species were considerably lower. 5. Relatively high concentrations of nonmethylene-interrupted fatty acids were detected in certain examined species.

Animals↗
PubMed1995

Separation of major polar lipids in Pecten maximus by high-performance liquid chromatography and subsequent determination of their fatty acids using gas chromatography.

An easy method for the separation of major polar lipid classes by HPLC is described. Maximum resolution was achieved by an automated combination of a silica gel column and a diol column. Polar lipid analysis of the larvae and gonads of Pecten maximus showed the presence of a particular glycolipid especially rich in 22:6(n - 3) and the predominance of 20:4(n - 6) in the phosphatidylinositol. The phosphatidylcholine and phosphatidylethanolamine (diacyl form + alkenylacyl) were the major fractions. The plasmalogen form (25% in larvae, 34% in gonads) was essentially composed of polyunsaturated fatty acids of 20 and 22 carbons in the sn-2 position.

Animals↗
PubMed1996

Ontogenic development of membrane lipids in the chick optic lobe.

The developmental profiles of the lipid composition and their de novo synthesis and remodelling in the optic lobe of the chicken were studied. The 32P incorporation to phospholipids showed an active de novo synthesis mainly of phosphatidylinositol and of a particular fraction of phosphatidylcholine during the early stages of the embryo development, concomitantly with the beginning of synaptogenesis. This de novo synthesis of phospholipids strongly increased at hatching. On the other hand, phosphatidylinositol presented an active lipid exchange (acylation-deacylation) in the early stages of embryogenesis, indicating a strong incorporation of 14C-arachidonic acid during this period, followed by a fast drop in specific activity. Two different fractions of phosphatidylcholine were isolated by high-performance thin-layer chromatography with a different profile of fatty acid composition, disclosing their different physicochemical behavior, metabolic activities and evolution during embryogenesis. 32P incorporation into phosphatidylethanolamine remained very low during the earliest stages of embryogenesis, showing an increase when the process of synaptogenesis began, until hatching, when radioactivity reached a plateau. 14C-arachidonic acid incorporation into phosphatidylethanolamine was minimal. Furthermore, the phosphatidylethanolamine pool was progressively enriched in its ethanolamine plasmalogen throughout the development. Chromatographic analysis of lipid extracts showed the presence of cerebroside traces after 16 days of embryo incubation. At hatching, a remarkable increase in non-hydroxylated cerebrosides was observed concurrently with the appearance of hydroxylated ones. These glycosphingolipids, as well as the sulfatides, were markedly increased in the lipid extracts of optic lobes of adult animals, indicating the progressive development and maturity of the myelin sheath.

Animals↗
PubMedDate not supplied

Myopathy in an infant with a fatal peroxisomal disorder.

An infant with neonatal adrenoleukodystrophy experienced extreme hypotonia and virtually continuous convulsions at four months of age and died. Light and electron microscopic examination revealed evidence of myopathy and the presence of mitochondrial inclusions. Concentrations of very long-chain fatty acids were elevated in blood and fibroblasts and the oxidation of 14C-labeled fatty acids was defective. Urinary pipecolic acid content was increased. Activity of the peroxisomal dihydroxyacetone phosphate acyltransferase, which catalyzes the first step in plasmalogen synthesis, was decreased.

Acyltransferases↗
PubMed1991

Peroxisomes of normal morphology but deficient in 3-oxoacyl-CoA thiolase in rhizomelic chondrodysplasia punctata fibroblasts.

Rhizomelic Chondrodysplasia Punctata (RCDP) is an autosomal recessive disorder in which plasmalogen biosynthesis and phytanate catabolism are impaired. Peroxisomal structure and the intracellular localization of catalase, the 69 kDa peroxisomal integral membrane protein (PMP), and 3-oxoacyl-CoA thiolase were studied in cultured skin fibroblasts from control subjects and patients with RCDP. A punctate fluorescence pattern characteristic for peroxisomes was seen in control cells incubated with either anti-(catalase), anti-(69 kDa PMP) or anti-(3-oxoacyl-CoA thiolase). Incubation of mutant cells with anti-(catalase) or anti-(69 kDa PMP) resulted in the same pattern. However, when RCDP fibroblasts were incubated with a monoclonal anti-(3-oxoacyl-CoA thiolase) antibody no punctate fluorescence could be observed. Cryosections from control and RCDP cells were examined by electron microscopy using double immunogold labelling. RCDP fibroblasts contained structures indistinguishable from control peroxisomes, the membranes reacting with anti-(69 kDa PMP) and the matrix with anti-(catalase). However, the matrix of RCDP peroxisomes, unlike control peroxisomes, did not react with anti-(3-oxoacyl-CoA thiolase). We conclude that RCDP fibroblasts contain regularly shaped peroxisomes, comparable to control peroxisomes in number as well as in content of catalase and 69 kDa PMP. However, in RCDP peroxisomes the amount of 3-oxoacyl-CoA thiolase protein proved to be below the limit of detection.

Acetyl-CoA C-Acetyltransferase↗