scholarly journals Cell membranes. Molecular lipid therapy

2017 ◽  
Vol 71 ◽  
pp. 1239-1250
Author(s):  
Anna Walczewska ◽  
Barbara Dziedzic ◽  
Dawid Stulczewski ◽  
Emilia Zgórzyńska
Keyword(s):  
Lipid Composition ◽  
Protein Function ◽  
Membrane Lipids ◽  
Transmembrane Protein ◽  
Functional Characteristic ◽  
Membrane Lipid ◽  
Molecular Structures ◽  
Membrane Microdomains ◽  
Membrane Lipid Composition ◽  
Wide Range

Membrane lipids, due to diverse molecular structures, electric charge and different functional characteristic, have a profound role in multiple cytophysiological processes. A better understanding of the membrane structure and changes of its function in a wide range of diseases gave rise to a new approach termed membrane lipid therapy and directed to modifying the membranes. The strategies directed to membrane involve a direct regulation of membrane lipid composition that causes a change of the transmembrane protein function and modifies the organization of membrane microdomains, or regulation of enzyme activity and gene expression to alter membrane lipid composition. Membrane therapy assumes the use of new molecules specifically designed to modify lipid composition and function of abnormal signaling proteins. Therefore, modifications of the lipid composition and organization of membrane microdomains become pharmacological targets to reverse pathological changes in the profile of enzymatically and non-enzymatically generated lipid derivatives or to modify signaling pathways in the cell. The present monography is an update of the canonical membrane model by Singer-Nicolson and describes the therapeutic targets related to the regulation of the composition and organization of the lipids in the plasma membrane.

scholarly journals Membrane Lipid Composition of the Moderately Thermophilic Ammonia-Oxidizing Archaeon “Candidatus Nitrosotenuis uzonensis” at Different Growth Temperatures

2019 ◽  
Vol 85 (20) ◽  
Author(s):  
Nicole J. Bale ◽  
Marton Palatinszky ◽  
W. Irene C. Rijpstra ◽  
Craig W. Herbold ◽  
Michael Wagner ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Strong Influence ◽  
Thermal Spring ◽  
Membrane Lipid ◽  
Effect Of Temperature ◽  
Environmental Niche ◽  
Membrane Lipid Composition ◽  
Moderately Thermophilic ◽  
Wide Range ◽  
Membrane Spanning

ABSTRACT “Candidatus Nitrosotenuis uzonensis” is the only cultured moderately thermophilic member of the thaumarchaeotal order Nitrosopumilales (NP) that contains many mesophilic marine strains. We examined its membrane lipid composition at different growth temperatures (37°C, 46°C, and 50°C). Its lipids were all membrane-spanning glycerol dialkyl glycerol tetraethers (GDGTs), with 0 to 4 cyclopentane moieties. Crenarchaeol (cren), the characteristic thaumarchaeotal GDGT, and its isomer (crenʹ) were present in high abundance (30 to 70%). The GDGT polar headgroups were mono-, di-, and trihexoses and hexose/phosphohexose. The ratio of glycolipid to phospholipid GDGTs was highest in the cultures grown at 50°C. With increasing growth temperatures, the relative contributions of cren and crenʹ increased, while those of GDGT-0 to GDGT-4 (including isomers) decreased. TEX86 (tetraether index of tetraethers consisting of 86 carbons)-derived temperatures were much lower than the actual growth temperatures, further demonstrating that TEX86 does not accurately reflect the membrane lipid adaptation of thermophilic Thaumarchaeota. As the temperature increased, specific GDGTs changed relative to their isomers, possibly representing temperature adaption-induced changes in cyclopentane ring stereochemistry. Comparison of a wide range of thaumarchaeotal core lipid compositions revealed that the “Ca. Nitrosotenuis uzonensis” cultures clustered separately from other members of the NP order and the Nitrososphaerales (NS) order. While phylogeny generally seems to have a strong influence on GDGT distribution, our analysis of “Ca. Nitrosotenuis uzonensis” demonstrates that its terrestrial, higher-temperature niche has led to a lipid composition that clearly differentiates it from other NP members and that this difference is mostly driven by its high crenʹ content. IMPORTANCE For Thaumarchaeota, the ratio of their glycerol dialkyl glycerol tetraether (GDGT) lipids depends on growth temperature, a premise that forms the basis of the widely applied TEX86 paleotemperature proxy. A thorough understanding of which GDGTs are produced by which Thaumarchaeota and what the effect of temperature is on their GDGT composition is essential for constraining the TEX86 proxy. “Ca. Nitrosotenuis uzonensis” is a moderately thermophilic thaumarchaeote enriched from a thermal spring, setting it apart in its environmental niche from the other marine mesophilic members of its order. Indeed, we found that the GDGT composition of “Ca. Nitrosotenuis uzonensis” cultures was distinct from those of other members of its order and was more similar to those of other thermophilic, terrestrial Thaumarchaeota. This suggests that while phylogeny has a strong influence on GDGT distribution, the environmental niche that a thaumarchaeote inhabits also shapes its GDGT composition.

scholarly journals Effect of membrane environment on the activity and inhibitability by malonyl-CoA of the carnitine acyltransferase of hepatic microsomal membranes

1997 ◽  
Vol 322 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Neil M. BROADWAY ◽  
E. David SAGGERSON
Keyword(s):  
Lipid Composition ◽  
Membrane Lipids ◽  
Specific Activity ◽  
Membrane Lipid ◽  
Microsomal Membrane ◽  
Membrane Lipid Composition ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Microsomal Membranes ◽  
Myristoyl Coa

We have investigated the extent to which membrane environment affects the catalytic properties of the malonyl-CoA-sensitive carnitine acyltransferase of liver microsomal membranes. Arrhenius-type plots of activity were linear in the absence and presence of malonyl-CoA (2.5 μM). Sensitivity to malonyl-CoA increased with decreasing assay temperature. Partly purified enzyme displayed an increased K0.5 (substrate concentration supporting half the maximal reaction rate) for myristoyl-CoA and a reduced sensitivity to malonyl-CoA compared with the enzyme in situ in membranes. Reconstitution with liposomes of a range of compositions restored the K0.5 for myristoyl-CoA to values similar to that seen in native membranes. The lipid requirements for restoration of sensitivity to malonyl-CoA were more stringent. When animals were starved for 24 h the specific activity of carnitine acyltransferase in microsomal membrane residues was increased 3.3-fold, whereas sensitivity to malonyl-CoA was decreased to 1/2.8. When enzymes partly purified from fed and starved animals were reconstituted into crude soybean phosphatidylcholine liposomes there was no difference in sensitivity to malonyl-CoA. When partly purified enzyme from fed rats was reconstituted into liposomes prepared from microsomal membrane lipids from fed animals it was 2.2-fold more sensitive to malonyl-CoA than when reconstituted with liposomes prepared from microsomal membrane lipids from starved animals. This suggests that the physiological changes in sensitivity to malonyl-CoA are mediated via changes in membrane lipid composition rather than via modification of the enzyme protein itself. The increased specific actvity of acyltransferase observed on starvation could not be attributed to changes in membrane lipid composition.

scholarly journals Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 919
Author(s):  
Manuel Torres ◽  
Sebastià Parets ◽  
Javier Fernández-Díaz ◽  
Roberto Beteta-Göbel ◽  
Raquel Rodríguez-Lorca ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Therapeutic Potential ◽  
Membrane Lipid ◽  
Fatty Acyl ◽  
Bioactive Lipids ◽  
Membrane Lipid Composition ◽  
Membrane Structure And Function ◽  
And Function

Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).

scholarly journals Intact Membrane Lipids of “Candidatus Nitrosopumilus maritimus,” a Cultivated Representative of the Cosmopolitan Mesophilic Group I Crenarchaeota

2008 ◽  
Vol 74 (8) ◽  
pp. 2433-2440 ◽  
Author(s):  
Stefan Schouten ◽  
Ellen C. Hopmans ◽  
Marianne Baas ◽  
Henry Boumann ◽  
Sonja Standfest ◽  
...  
Keyword(s):  
Polar Lipid ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Lipid Analysis ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
The Core ◽  
Group I ◽  
Head Groups ◽  
Intact Membrane

ABSTRACT In this study we analyzed the membrane lipid composition of “Candidatus Nitrosopumilus maritimus,” the only cultivated representative of the cosmopolitan group I crenarchaeota and the only mesophilic isolate of the phylum Crenarchaeota. The core lipids of “Ca. Nitrosopumilus maritimus” consisted of glycerol dialkyl glycerol tetraethers (GDGTs) with zero to four cyclopentyl moieties. Crenarchaeol, a unique GDGT containing a cyclohexyl moiety in addition to four cyclopentyl moieties, was the most abundant GDGT. This confirms unambiguously that crenarchaeol is synthesized by species belonging to the group I.1a crenarchaeota. Intact polar lipid analysis revealed that the GDGTs have hexose, dihexose, and/or phosphohexose head groups. Similar polar lipids were previously found in deeply buried sediments from the Peru margin, suggesting that they were in part synthesized by group I crenarchaeota.

scholarly journals Membrane Synthesis, Specific Lipid Requirements, and Localized Lipid Composition Changes Associated with a Positive-Strand RNA Virus RNA Replication Protein

2003 ◽  
Vol 77 (23) ◽  
pp. 12819-12828 ◽  
Author(s):  
Wai-Ming Lee ◽  
Paul Ahlquist
Keyword(s):  
Lipid Composition ◽  
Rna Synthesis ◽  
Membrane Lipids ◽  
Rna Virus ◽  
Rna Replication ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna ◽  
Total Membrane

ABSTRACT Multifunctional RNA replication protein 1a of brome mosaic virus (BMV), a positive-strand RNA virus, localizes to the cytoplasmic face of endoplasmic reticulum (ER) membranes and induces ER lumenal spherules in which viral RNA synthesis occurs. We previously showed that BMV RNA replication in yeast is severely inhibited prior to negative-strand RNA synthesis by a single-amino-acid substitution in the ole1w allele of yeast Δ9 fatty acid (FA) desaturase, which converts saturated FAs (SFAs) to unsaturated FAs (UFAs). Here we further define the relationships between 1a, membrane lipid composition, and RNA synthesis. We show that 1a expression increases total membrane lipids in wild-type (wt) yeast by 25 to 33%, consistent with recent results indicating that the numerous 1a-induced spherules are enveloped by invaginations of the outer ER membrane. 1a did not alter total membrane lipid composition in wt or ole1w yeast, but the ole1w mutation selectively depleted 18-carbon, monounsaturated (18:1) FA chains and increased 16:0 SFA chains, reducing the UFA-to-SFA ratio from ∼2.5 to ∼1.5. Thus, ole1w inhibition of RNA replication was correlated with decreased levels of UFA, membrane fluidity, and plasticity. The ole1w mutation did not alter 1a-induced membrane synthesis, 1a localization to the perinuclear ER, or colocalization of BMV 2a polymerase, nor did it block spherule formation. Moreover, BMV RNA replication templates were still recovered from cell lysates in a 1a-induced, 1a- and membrane-associated, and nuclease-resistant but detergent-susceptible state consistent with spherules. However, unlike nearby ER membranes, the membranes surrounding spherules in ole1w cells were not distinctively stained with osmium tetroxide, which interacts specifically with UFA double bonds. Thus, in ole1w cells, spherule-associated membranes were locally depleted in UFAs. This localized UFA depletion helps to explain why BMV RNA replication is more sensitive than cell growth to reduced UFA levels. The results imply that 1a preferentially interacts with one or more types of membrane lipids.

scholarly journals Heat Adaptation Alters Escherichia coli O157:H7 Membrane Lipid Composition and Verotoxin Production

2003 ◽  
Vol 69 (9) ◽  
pp. 5115-5119 ◽  
Author(s):  
Hyun-Gyun Yuk ◽  
Douglas L. Marshall
Keyword(s):  
Escherichia Coli ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Vaccenic Acid ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
E Coli ◽  
Heat Adaptation ◽  
Mutant Strains ◽  
Composition Changes

ABSTRACT The influence of heat adaptation (growth at 42 and 45°C) on changes in membrane lipid composition and verotoxin concentration of Escherichia coli O157:H7 (ATCC 43895), an rpoS mutant of ATCC 43895 (FRIK 816-3), a verotoxin mutant E. coli O157:H7 (B6-914), and nonpathogenic E. coli (ATCC 25922) was investigated. D values (57°C) of heat-adapted cells were up to 3.9 min longer than those of control cells for all four strains. Heat adaptation increased the amounts of palmitic acid (16:0) and cis-vaccenic acid (18:1ω7c) in membrane lipids of ATCC 43895 and the rpoS mutant, whereas there was a reduction and no change in the amount of cis-vaccenic acid in nonpathogenic and verotoxin mutant E. coli, respectively. The ratio of palmitic to cis-vaccenic acids decreased in ATCC 43895 and in the rpoS mutant, whereas the ratio increased in nonpathogenic E. coli and was not different in the verotoxin mutant with elevated growth temperature. Total verotoxin concentration decreased due to a reduction in intracellular verotoxin amount in heat-adapted ATCC 43895 and rpoS mutant strains. However, extracellular verotoxin concentration increased in heat-adapted cells. The rpoS gene did not influence membrane lipid composition changes although it did affect heat resistance. Results suggest that increased membrane fluidity may have caused increased verotoxin secretion.

Ontogeny of basolateral membrane lipid composition and fluidity in small intestine

1989 ◽  
Vol 257 (1) ◽  
pp. G138-G144 ◽  
Author(s):  
S. M. Schwarz ◽  
H. E. Bostwick ◽  
M. D. Danziger ◽  
L. J. Newman ◽  
M. S. Medow
Keyword(s):  
Lipid Composition ◽  
Protein Function ◽  
Specific Activity ◽  
Lipid Analysis ◽  
Basolateral Membrane ◽  
Age Groups ◽  
Membrane Lipid ◽  
Fatty Acyl ◽  
Membrane Lipid Composition ◽  
Small Intestinal

To evaluate physicochemical properties of the small intestinal basolateral cell surface during postnatal development, membranes were isolated from suckling (14-17 days) and weanling-mature (35-49 days) rabbit jejunal and ileal enterocytes at 30- to 40-fold purification (based on Na+-K+-ATPase specific activity) and with limited contamination from coisolated cellular elements. Membrane lipid analysis demonstrated age-dependent reductions and proximal to distal increases in total lipid (per milligram protein). Postnatal increases in membrane total cholesterol of jejunum (suckling vs. mature, 0.18 vs. 0.26 mumol/mg protein; P less than 0.01) and ileum (0.18 vs. 0.31 mumol/mg protein; P less than 0.01) resulted in markedly higher cholesterol-to-phospholipid molar ratios (jejunum, 0.43 vs. 0.73; ileum, 0.43 vs. 0.72 mumol/mg protein; P less than 0.01). Membranes from mature animals had higher relative sphingomeylin and phosphatidylcholine content and, in both age groups, fatty acyl saturation was increased in ileum compared with jejunum. By utilization of the fluorophores 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, the fluidity of basolateral membranes and liposomes prepared from extracted membrane lipid decreased markedly in mature rabbits. Arrhenius plots demonstrated higher apparent thermotropic transition temperatures of mature membrane lipid. These data therefore demonstrate significant changes in small intestinal basolateral membrane lipid composition and fluidity that occur during the weaning period. Possible relationships to ontogenesis of membrane protein function are discussed.

scholarly journals Class II PI3Ks at the Intersection between Signal Transduction and Membrane Trafficking

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 104 ◽  
Author(s):  
Jean Piero Margaria ◽  
Edoardo Ratto ◽  
Luca Gozzelino ◽  
Huayi Li ◽  
Emilio Hirsch
Keyword(s):  
Signal Transduction ◽  
Membrane Trafficking ◽  
Lipid Composition ◽  
Intracellular Signaling ◽  
Class Ii ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Inositol Phospholipids ◽  
Wide Range ◽  
And Migration

Phosphorylation of inositol phospholipids by the family of phosphoinositide 3-kinases (PI3Ks) is crucial in controlling membrane lipid composition and regulating a wide range of intracellular processes, which include signal transduction and vesicular trafficking. In spite of the extensive knowledge on class I PI3Ks, recent advances in the study of the three class II PI3Ks (PIK3C2A, PIK3C2B and PIK3C2G) reveal their distinct and non-overlapping cellular roles and localizations. By finely tuning membrane lipid composition in time and space among different cellular compartments, this class of enzymes controls many cellular processes, such as proliferation, survival and migration. This review focuses on the recent developments regarding the coordination of membrane trafficking and intracellular signaling of class II PI3Ks through the confined phosphorylation of inositol phospholipids.

scholarly journals Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4212 ◽  
Author(s):  
Christine Hellwing ◽  
Axel Schoeniger ◽  
Claudia Roessler ◽  
Anja Leimert ◽  
Julia Schumann
Keyword(s):  
Fatty Acids ◽  
Lipid Rafts ◽  
Lipid Composition ◽  
Membrane Lipid ◽  
Receptor Expression ◽  
Membrane Microdomains ◽  
Pufa Supplementation ◽  
Membrane Lipid Composition ◽  
Membrane Microdomain ◽  
Raw264.7 Macrophages

BackgroundToll like receptors (TLRs) are an important and evolutionary conserved class of pattern recognition receptors associated with innate immunity. The recognition of Gram-positive cell wall constituents strongly depends on TLR2. In order to be functional, TLR2 predominantly forms a heterodimer with TLR1 or TLR6 within specialized membrane microdomains, the lipid rafts. The membrane lipid composition and the physicochemical properties of lipid rafts are subject to modification by exogenous fatty acids. Previous investigations of our group provide evidence that macrophage enrichment with polyunsaturated fatty acids (PUFA) induces a reordering of lipid rafts and non-rafts based on the incorporation of supplemented PUFA as well as their elongation and desaturation products.MethodsIn the present study we investigated potential constraining effects of membrane microdomain reorganization on the clustering of TLR2 with its co-receptors TLR1 and TLR6 within lipid rafts. To this end, RAW264.7 macrophages were supplemented with either docosahexaenoic acid (DHA) or arachidonic acid (AA) and analyzed for receptor expression and microdomain localization in context of TLR stimulation.Results and ConclusionsOur analyses showed that receptor levels and microdomain localization were unchanged by PUFA supplementation. The TLR2 pathway, in contrast to the TLR4 signaling cascade, is not affected by exogenous PUFA at the membrane level.

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