scholarly journals Convergence of Multiple Stimuli to a Single Gate in TREK1 and TRAAK Potassium Channels

2021 ◽  
Vol 12 ◽  
Author(s):  
Frank S Choveau ◽  
Ismail Ben Soussia ◽  
Delphine Bichet ◽  
Chatelain C. Franck ◽  
Sylvain Feliciangeli ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Potassium Channels ◽  
Polyunsaturated Fatty Acids ◽  
Extracellular Ph ◽  
Channel Activity ◽  
Membrane Stretch ◽  
State Dependent ◽  
The Subject ◽  
Intense Research

Inhibitory potassium channels of the TREK1/TRAAK family are integrators of multiple stimuli, including temperature, membrane stretch, polyunsaturated fatty acids and pH. How these signals affect the gating of these channels is the subject of intense research. We have previously identified a cytoplasmic domain, pCt, which plays a major role in controlling channel activity. Here, we use pharmacology to show that the effects of pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Using a state-dependent inhibitor, fluoxetine, as well as natural and synthetic openers, we provide further evidence that the “up” and “down” conformations identified by crystallography do not correspond to open and closed states of these channels.

scholarly journals Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane

1988 ◽  
Vol 253 (2) ◽  
pp. 417-424 ◽  
Author(s):  
C J Field ◽  
E A Ryan ◽  
A B Thomson ◽  
M T Clandinin
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Insulin Binding ◽  
Fatty Acyl ◽  
Membrane Composition ◽  
Membrane Phospholipids ◽  
Diabetic State

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte.

scholarly journals Production of Microbial Lipids Containing Arachidonic Acid and Its Related Polyunsaturated Fatty Acids

Oleoscience ◽  
2012 ◽  
Vol 12 (7) ◽  
pp. 263-272
Author(s):  
Eiji SAKURADANI ◽  
Akinori ANDO ◽  
Sakayu SHIMIZU ◽  
Jun OGAWA
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Microbial Lipids

scholarly journals Selective internalization of arachidonic acid by endothelial cells

1987 ◽  
Vol 245 (1) ◽  
pp. 151-157 ◽  
Author(s):  
E R Hall ◽  
C E Manner ◽  
J Carinhas ◽  
R Snopko ◽  
M Rafelson
Keyword(s):  
Fatty Acids ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Endothelial Cell ◽  
Polyunsaturated Fatty Acids ◽  
Cell Types ◽  
Time Dependent ◽  
Asymmetric Distribution ◽  
Membrane Phospholipids ◽  
Bovine Endothelial Cell

The asymmetric distribution of phospholipids in bovine endothelial-cell membranes was probed with 2,4,6-trinitrobenzenesulphonate and purified phospholipase A2. The data suggest that phosphotidylethanolamine is primarily located in the inner lipid bilayer, as reported for other cell types. Stearic acid is taken up by the endothelial cells and is randomly distributed among the membrane phospholipids. In contrast, the polyunsaturated fatty acids (arachidonic, eicosatrienoic and eicosapentaenoic acids) have initial incorporation into the phosphatidylcholine fraction. These fatty acids then undergo a time-dependent transfer from phosphatidylcholine to phosphatidylethanolamine. Thus we propose that endothelial cells possess a mechanism for the selective internalization of polyunsaturated fatty acids.

scholarly journals Some Biogenetic Considerations Regarding the Marine Natural Product (−)-Mucosin

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4147 ◽  
Author(s):  
Jens M. J. Nolsøe ◽  
Marius Aursnes ◽  
Yngve H. Stenstrøm ◽  
Trond V. Hansen
Keyword(s):  
Fatty Acids ◽  
Natural Products ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Natural Product ◽  
Polyunsaturated Fatty Acid ◽  
Marine Natural Product ◽  
Structural Pattern ◽  
Different Origin

Recently, the identity of the marine hydrindane natural product (−)-mucosin was revised to the trans-fused structure 6, thereby providing a biogenetic puzzle that remains to be solved. We are now disseminating some of our insights with regard to the possible machinery delivering the established architecture. Aspects with regard to various modes of cyclization in terms of concerted versus stepwise processes are held up against the enzymatic apparatus known to be working on arachidonic acid (8). To provide a contrast to the tentative polyunsaturated fatty acid biogenesis, the structural pattern featured in (−)-mucosin (6) is compared to some marine hydrinane natural products of professed polyketide descent. Our appraisal points to a different origin and strengthens the hypothesis of a polyunsaturated fatty acids (PUFA) as the progenitor of (−)-mucosin (6).

scholarly journals Prediagnostic plasma polyunsaturated fatty acids and the risk of amyotrophic lateral sclerosis

Neurology ◽  
2019 ◽  
Vol 94 (8) ◽  
pp. e811-e819 ◽  
Author(s):  
Éilis J. O'Reilly ◽  
Kjetil Bjornevik ◽  
Jeremy D. Furtado ◽  
Laurence N. Kolonel ◽  
Loic Le Marchand ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Amyotrophic Lateral Sclerosis ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Conditional Logistic Regression ◽  
Gas Liquid Chromatography ◽  
Blood Draw ◽  
Total N ◽  
Bottom Quartile ◽  
Lateral Sclerosis

ObjectiveTo examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS).MethodsWe identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS.ResultsThere was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men.ConclusionsThe majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.

scholarly journals Identification of Genetic Loci Associated with Plasma Long-chain Polyunsaturated Fatty Acids in Hispanic Children (P08-129-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ruixue Hou ◽  
Shelley Cole ◽  
Karin Haack ◽  
Sandra Laston ◽  
Nitesh Mehta ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Plasma Levels ◽  
Transmembrane Protein ◽  
Snp Array ◽  
Chromosome 11 ◽  
Hispanic Children ◽  
Genome Wide ◽  
Long Chain

Abstract Objectives Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical to the functioning of cell membranes as important constituents of phospholipids. They also serve as precursors for prostaglandins, leukotrienes and thromboxanes which affect metabolic processes such as vasodilation, inflammation and cell proliferation. The objective of this study was to identify genes that influence the plasma levels of LC-PUFAs in Hispanic children of the Viva La Familia study. Methods Plasma levels of LC-PUFAs, including eicosapentanoic acid (EPA, 20:5, n-3), docosahexanoic acid (DHA, 22:6, n-3), docosapentanoic acid (DPA, 22:5, n-3), arachidonic acid (20: 4 n-6) and docosapentanoic acid (DPA, 22:5 n-6), were measured as part of metabolomics profiling. Genome-wide single nucleotide polymorphisms (SNP) (array and exome sequence) association analysis (GWAS) were conducted using additive genetic models adjusting for kinships. Results GWAS identified several loci on chromosome 11 with significant evidence of association with LC-PUFAs. These include association of EPA and arachidonic acid with rs174548, rs174545, rs174546, rs174550, 1rs74538 of fatty acid desaturase 1 (FADS1), rs1535, rs174577, rs174568, 174570, 2072114, 2727270 of FADS2, rs174538 of flap structure-specific endonuclease 1 (FEN1), rs174535, rs174528, rs198462, rs174532, rs149803 and rs198464 of myelin regulatory factor (MYRF) and rs102275 and rs102274 of transmembrane protein 258 (TMEM258) (P < 10−12, MAF 5–45%). Other LC-PUFAs showed suggestive evidence of association with the same SNPs. Except for FADS2 SNPs, carriers of minor alleles of all other identified SNPs had lower levels of EPA and arachidonic acid with effect sizes ranging from 5–10%. The analysis of exome variants revealed significant association of EPA with two novel SNPs in syphingomyelin synthase 2 (SGMS2) (P = 1.6 × 10−8) and synaptotagmin 7 (SYT7) (<3 × 10−15, MAF 1.5–33%). The same two loci were associated with arachidonic acid (<6 × 10−9). No significant or suggestive associations were found for other LC-PUFAs. Conclusions In summary, our genome-wide and exome sequencing results replicated the association of EPA and arachidonic acid with FADS and TMEM258 genes and identified novel loci related to neuronal signaling mainly in MYRF, SGMS2 and SYT7. Funding Sources National Institutes of Health (NIH) [DK080457], and the USDA/ARS [Cooperative Agreement 6250-51000-053].

scholarly journals Resistance of Biomphalaria alexandrina to Schistosoma mansoni and Bulinus truncatus to Schistosoma haematobium Correlates with Unsaturated Fatty Acid Levels in the Snail Soft Tissue

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Marian Elias ◽  
Rasha S. Hanafi ◽  
Samia El-Bardicy ◽  
Ebtisam A. Hafez ◽  
Rashika El Ridi
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Soft Tissue ◽  
Polyunsaturated Fatty Acids ◽  
Schistosoma Mansoni ◽  
Schistosome Infection ◽  
Bulinus Truncatus ◽  
Biomphalaria Alexandrina ◽  
Arachidonic Acids

Only a fraction of the Biomphalaria and Bulinus snail community shows patent infection with schistosomes despite continuous exposure to the parasite, indicating that a substantial proportion of snails may resist infection. Accordingly, exterminating the schistosome intermediate snail hosts in transmission foci in habitats that may extend to kilometres is cost-prohibitive and damaging to the ecological equilibrium and quality of water and may be superfluous. It may be more cost effective with risk less ecological damage to focus on discovering the parameters governing snail susceptibility and resistance to schistosome infection. Therefore, laboratory bred Biomphalaria alexandrina and Bulinus truncatus snails were exposed to miracidia of laboratory-maintained Schistosoma mansoni and S. haematobium, respectively. Snails were examined for presence or lack of infection association with soft tissue and hemolymph content of proteins, cholesterol, and triglycerides, evaluated using standard biochemical techniques and palmitic, oleic, linoleic, and arachidonic acid, assayed by ultraperformance liquid chromatography-tandem mass spectrometry. Successful schistosome infection of B. alexandrina and B. truncatus consistently and reproducibly correlated with snails showing highly significant (up to P < 0.0001 ) decrease in soft tissue and hemolymph content of the monounsaturated fatty acid, oleic acid, and the polyunsaturated fatty acids, linoleic, and arachidonic acids as compared to naïve snails. Snails that resisted twice infection had soft tissue content of oleic, linoleic, and arachidonic acid similar to naïve counterparts. High levels of soft tissue and hemolymph oleic, linoleic, and arachidonic acid content appear to interfere with schistosome development in snails. Diet manipulation directed to eliciting excessive increase of polyunsaturated fatty acids in snails may protect them from infection and interrupt disease transmission in a simple and effective manner.

Functional analysis of rat liver citrate carrier promoter: differential responsiveness to polyunsaturated fatty acids

2008 ◽  
Vol 417 (2) ◽  
pp. 561-571 ◽  
Author(s):  
Fabrizio Damiano ◽  
Gabriele V. Gnoni ◽  
Luisa Siculella
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Luciferase Reporter ◽  
H4iie Cells ◽  
E Box ◽  
Citrate Carrier ◽  
Response Region

CiC (citrate carrier), a mitochondrial membrane protein, plays an important metabolic role by transporting acetyl-CoA into the cytosol for fatty acid and cholesterol synthesis. Several studies showed that CiC activity and expression is regulated by dietary fatty acids. In the present study we report data on the structural and functional characterization of the 5′-flanking region of the rat Cic gene. By transient transfection assays in H4IIE rat hepatoma cells, a PUFA (polyunsaturated fatty acids) response region has been identified within the CiC promoter. A cluster of putative binding sites for several transcription factors, composed of a NF-Y (nuclear factor-Y) site, an E-box-like site, a SRE1 (sterol regulatory element 1)-like site and four Sp1 (stimulatory protein 1) sites, was localized in the promoter region. Luciferase reporter gene and gel mobility shift assays indicated that a functional E-box-like, essential to the basal CiC promoter activity, confers responsiveness to activation by SREBP (SRE-binding protein)-1c. This study provides evidence for SREBP-1c as a principal target for PUFA regulation of CiC transcription. In H4IIE cells, overexpression of nSREBP (nuclear SREBP)-1c over-rides arachidonic acid (C20:4, n-6) suppression, but does not prevent the repression by docosahexaenoic acid (C22:6, n-3). ChIP (chromatin immunoprecipitation) assays in H4IIE cells showed that docosahexaenoic acid affects the binding of NF-Y, Sp1 and SREBP-1 to the PUFA response region of CiC promoter, whereas arachidonic acid alters only the binding of SREBP-1. Our data show that PUFA inhibition of hepatic Cic gene transcription is mediated not only by the nuclear level of SREBP-1c, but also might involve a reduction in Sp1 and NF-Y DNA binding, suggesting differential mechanisms in the Cic gene regulation by different PUFA.

scholarly journals Entry of polyunsaturated fatty acids into the brain: evidence that high-density lipoprotein-induced methylation of phosphatidylethanolamine and phospholipase A2 are involved

1996 ◽  
Vol 316 (3) ◽  
pp. 805-811 ◽  
Author(s):  
Valérie MAGRET ◽  
Latifa ELKHALIL ◽  
Françoise NAZIH-SANDERSON ◽  
Françoise MARTIN ◽  
Jean-Marie BOURRE ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
High Density Lipoprotein ◽  
Phospholipase A2 ◽  
Density Lipoprotein ◽  
Bovine Brain ◽  
High Density ◽  
Close Relationship ◽  
The Brain

The conversion of phosphatidylethanolamine (PE) into phosphatidylcholine (PC) by a sequence of three transmethylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL3) in isolated bovine brain capillary (BBC) membranes. HDL3-induced stimulation of BBC membranes pulsed with [methyl-14C]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC. PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A2 (PLA2), as demonstrated by the accumulation of lysophosphatidylcholine (lyso-PC). When PE containing [14C]arachidonic acid in the sn-2 position ([14C]PAPE) is incorporated into BBC membranes, HDL3 stimulation induces the formation of PMME, PDME, PC and lyso-PC and the release of [14C]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL3 stimulates a PLA2 that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA2 activities depend on a HDL3 concentration in the range 0–50 μg/ml and are strictly dependent on HDL3 binding, because HDL3 modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA2 activation. Moreover, HDL3 prelabelled with [14C]PAPE can stimulate PDME and lyso-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL3 can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL3 binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.

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