Eosinophil polyunsaturated fatty acid metabolism and its potential control of inflammation and allergy

AbstractPolyunsaturated fatty acids (PUFAs) exhibit a range of biological effects, many of which are mediated through the formation and actions of their bioactive metabolites. It is well appreciated that dietary PUFA balance affects inflammation and/or allergic diseases, and recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS)-based mediator lipidomics have revealed a potential link between PUFA metabolism and biological phenotypes. This review presents insights into the emerging roles of eosinophil PUFA metabolism in controlling inflammatory responses and its potential involvement in allergy control

Comprehensive identification of sphingolipid species by in silico retention time and tandem mass spectral library

Additional file 1. Figure S1 The fragment assignments of 12 sphingolipid classes. The annotations were combinatorially performed by hydrogen rearrangement rules in combination with substantial manual curation. The original spectra were obtained from LC/MS data of some biological samples including human cells, mouse tissues, and plant species

Endogenous Receptor Agonists: Resolving Inflammation

Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA)–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution

18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload–induced maladaptive cardiac remodeling

N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit, although the mechanisms underlying this effect remain poorly understood. Fat-1 transgenic mice expressing Caenorhabditis elegans n-3 fatty acid desaturase, which is capable of producing n-3 PUFAs from n-6 PUFAs, exhibited resistance to pressure overload–induced inflammation and fibrosis, as well as reduced cardiac function. Lipidomic analysis revealed selective enrichment of eicosapentaenoic acid (EPA) in fat-1 transgenic bone marrow (BM) cells and EPA-metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. BM transplantation experiments revealed that fat-1 transgenic BM cells, but not fat-1 transgenic cardiac cells, contributed to the antiremodeling effect and that the 18-HEPE–rich milieu in the fat-1 transgenic heart was generated by BM-derived cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated proinflammatory activation of cardiac fibroblasts in culture, and in vivo administration of 18-HEPE reproduced the fat-1 mice phenotype, including resistance to pressure overload–induced maladaptive cardiac remodeling

Resolvins as Regulators of the Immune System

Inflammation is the first response of the immune system to infection or injury, but excessive or inappropriate inflammatory responses contribute to a range of acute and chronic human diseases. Clinical assessment of dietary supplementation of ω-3 polyunsaturated fatty acids (i.e., eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) indicate that they have beneficial impact on these diseases, although the mechanisms are poorly understood at the molecular level. In this decade, it has been revealed that EPA and DHA are enzymatically converted to bioactive metabolites in the course of acute inflammation and resolution. These metabolites were shown to regulate immune cell functions and to display potent anti-inflammatory actions both in vitro and in vivo. Because of their ability to resolve an acute inflammatory response, they are referred to as proresolving mediators, or resolvins. In this review, we provide an overview of the formation and actions of these lipid mediators

Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Abstractα-Tocopherol transfer protein (αTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by αTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and α-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-α-tocopherol=100%) calculated from the degree of competition were as follows: β-tocopherol, 38%; γ-tocopherol, 9%; δ-tocopherol, 2%; α-tocopherol acetate, 2%; α-tocopherol quinone, 2%; SRR-α-tocopherol, 11%; α-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for αTTP is one of the critical determinants of their biological activity

Amino acid sequence of heat-stable enterotoxin produced by Vibrio cholerae non-01

AbstractThe amino acid sequence of heat-stable enterotoxin, produced by Vibrio cholerae non-01 and isolated from its culture supernatant, was determined by both Edman degradation of native and reductively carboxy-methylated enterotoxin and also a combination of fast atom bombardment mass spectrometry and carboxy-peptidase Y digestion of native enterotoxin to be as follows: Ile-Asp-Cys-Cys-Glu-Ile-Cys-Cys-Asn-Pro-Ala-Cys-Phe-Gly-Cys-Leu-Asn. This sequence is very similar, but not identical, to those of heat-stable enterotoxins produced by enterotoxigenic Escherichia coli and Yersinia enterocolitica

Pleiotropic Roles of Cholesteryl Sulfate during Entamoeba Encystation: Involvement in Cell Rounding and Development of Membrane Impermeability

Entamoeba histolytica, a protozoan parasite, causes amoebiasis, which is a global public health problem. The major route of infection is oral ingestion of cysts, the only form that is able to transmit to a new host. Cysts are produced by cell differentiation from proliferative trophozoites in a process termed “encystation.” During encystation, cell morphology is markedly changed; motile amoeboid cells become rounded, nonmotile cells. Concomitantly, cell components change and significant fluctuations of metabolites occur. Cholesteryl sulfate (CS) is a crucial metabolite for encystation. However, its precise role remains uncertain. To address this issue, we used in vitro culture of Entamoeba invadens as the model system for the E. histolytica encystation study and identified serum-free culture conditions with CS supplementation at concentrations similar to intracellular CS concentrations during natural encystation. Using this culture system, we show that CS exerts pleiotropic effects during Entamoeba encystation, affecting cell rounding and development of membrane impermeability. CS dose dependently induced and maintained encysting cells as spherical maturing cysts with almost no phagocytosis activity. Consequently, the percentage of mature cysts was increased. CS treatment also caused time- and dose-dependent development of membrane impermeability in encysting cells via induction of de novo synthesis of dihydroceramides containing very long N-acyl chains ($26 carbons). These results indicate that CS-mediated morphological and physiological changes are necessary for the formation of mature cysts and the maintenance of the Entamoeba life cycle. Our findings also reveal important morphological aspects of the process of dormancy and the control of membrane structure

Hemispherical Net-structure Proximity Sensor Detecting Azimuth and Elevation for Guide Dog Robot

Abstract-We have developed a net-structure proximity sensor that detects the azimuth and elevation to a nearby object. This information can be used by robots to avoid obstacles or to respond to human behavior. We propose detection principles where the azimuth is detected by arranging two onedimensional net-structure proximity sensors along orthogonal axes, and the elevation is detected by arranging two onedimensional net-structure proximity sensors in a stacked ring. We also experimentally demonstrate the feasibility of these detection principles. The experimental result shows the sensor can detect azimuth at all peripheral angles and elevation from side to top up

Unbiased characterization of genotype-dependent metabolic regulations by metabolomic approach in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Metabolites are not only the catalytic products of enzymatic reactions but also the active regulators or the ultimate phenotype of metabolic homeostasis in highly complex cellular processes. The modes of regulation at the metabolome level can be revealed by metabolic networks. We investigated the metabolic network between wild-type and 2 mutant (<it>methionine-over accumulation 1 </it>[<it>mto1</it>] and <it>transparent testa4 </it>[<it>tt4</it>]) plants regarding the alteration of metabolite accumulation in <it>Arabidopsis thaliana</it>.</p> <p>Results</p> <p>In the GC-TOF/MS analysis, we acquired quantitative information regarding over 170 metabolites, which has been analyzed by a novel score (ZMC, z-score of metabolite correlation) describing a characteristic metabolite in terms of correlation. Although the 2 mutants revealed no apparent morphological abnormalities, the overall correlation values in <it>mto1 </it>were much lower than those of the wild-type and <it>tt4 </it>plants, indicating the loss of overall network stability due to the uncontrolled accumulation of methionine. In the <it>tt4 </it>mutant, a new correlation between malate and sinapate was observed although the levels of malate, sinapate, and sinapoylmalate remain unchanged, suggesting an adaptive reconfiguration of the network. Gene-expression correlations presumably responsible for these metabolic networks were determined using the metabolite correlations as clues.</p> <p>Conclusion</p> <p>Two Arabidopsis mutants, <it>mto1 </it>and <it>tt4</it>, exhibited the following changes in entire metabolome networks: the overall loss of metabolic stability (<it>mto1</it>) or the generation of a metabolic network of a backup pathway for the lost physiological functions (<it>tt4</it>). The expansion of metabolite correlation to gene-expression correlation provides detailed insights into the systemic understanding of the plant cellular process regarding metabolome and transcriptome.</p