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David Stanley - One of the best experts on this subject based on the ideXlab platform.
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prostaglandins and other Eicosanoids in insects biosynthesis and biological actions
Frontiers in Physiology, 2019Co-Authors: David StanleyAbstract:This essay reviews the discoveries, synthesis and biological significance of prostaglandins (PGs) and other Eicosanoids in insect biology. It presents the most current – and growing – understanding of the insect mechanism of PG biosynthesis, provide an updated treatment of known insect phospholipase A2 (PLA2), and detail contemporary findings on the biological roles of PGs and other Eicosanoids in insect physiology, including reproduction, fluid secretion, hormone actions in fat body, immunity and Eicosanoid signaling and cross-talk in immunity. It completes the essay with a prospectus meant to illuminate research opportunities for interested readers. In more detail, cellular and secretory types of PLA2, similar to those known on the biomedical background, have been identified in insects and their roles in Eicosanoid biosynthesis documented. It highlights recent findings showing that Eicosanoid biosynthetic pathway in insects is not identical to the solidly established biomedical picture. The relatively low concentrations of arachidonic acid (AA) present in insect phospholipids (< 0.1% in some species) indicate that PLA2 may hydrolyze linoleic acid (LA) as a precursor of Eicosanoid biosynthesis. The free LA is desaturated and elongated into AA. Unlike vertebrates, AA is not oxidized by cyclooxygenase, but by a specific peroxidase called peroxinectin to produce PGH2, which is then isomerized into cell-specific PGs. In particular, PGE2 synthase recently identified converts PGH2 into PGE2. In the cross-talks with other immune mediators, Eicosanoids act as downstream signals because any inhibition of Eicosanoid signaling leads to significant immunosuppression. Because host immunosuppression favors pathogens and parasitoids, some entomopathogens evolved a PLA2 inhibitory strategy activity to express their virulence.
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Eicosanoid-mediated immunity in insects
Developmental and Comparative Immunology, 2017Co-Authors: Shabbir Ahmed, David Stanley, Chunju AnAbstract:Abstract Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, Eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are propagated to nearly immune effectors such as hemocytes and fat body using various immune mediators, in which Eicosanoid signals act as the ultimate downstream mediator. The chemical diversity of Eicosanoids may operate to mediate various immune responses. Some entomopathogenic bacteria suppress Eicosanoid biosynthesis, which inhibits host insect immunity and promotes their pathogenicity. This review introduces immune responses mediated by various Eicosanoids. Then it explains the cross-talks of Eicosanoids with other immune mediators including cytokines, biogenic monoamines, and nitric oxide to clarify the complexity of insect immune mediation. Finally, we highlight the biological significance of Eicosanoids by demonstrating bacterial pathogenicity inhibiting a key enzyme – phospholipase A 2 – in Eicosanoid biosynthesis using their secondary metabolites to defend host insect immune attack.
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nitric oxide mediates insect cellular immunity via phospholipase a2 activation
Journal of Innate Immunity, 2017Co-Authors: David StanleyAbstract:After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, Eicosanoids, and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Separate treatments with an insect cytokine, 2 biogenic amines, and an Eicosanoid lead to a single result, hemocyte spreading, understood in terms of intracellular cross-talk among these signaling systems. This study focuses on the cross-talk between NO and Eicosanoid signaling in our model insect, Spodoptera exigua. Bacterial injection increased NO concentrations in the larval hemocytes and fat body, and RNA interference (RNAi) of the S. exigua NO synthase (NOS) gene suppressed NO concentrations. RNAi treatment also led to a significant reduction in hemocyte nodulation following bacterial injection. Similar RNAi treatments led to significantly reduced PLA2 activities in the hemocytes and fat body compared to control larvae. Injection of L-NAME also prevented the induction of PLA2 activity following bacterial challenge. An injected NO donor, S-nitroso-N-acetyl-DL-penicillamine, increased PLA2 activity in a dose-dependent manner. However, Eicosanoids did not influence NO concentrations in immune-challenged larvae. We infer that NO and Eicosanoid signaling operate via cross-talk mechanisms in which the elevated NO concentrations activate PLA2 and Eicosanoid biosynthesis, which finally mediates various immune responses.
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Inhibition of Eicosanoid signaling leads to increased lipid peroxidation in a host/parasitoid system
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2016Co-Authors: Ender Büyükgüzel, Hasan Tunaz, Meltem Erdem, Ceyhun Küçük, Utku Can Atılgan, David Stanley, Kemal BuyukguzelAbstract:Abstract We posed the hypothesis that inhibition of Eicosanoid biosynthesis leads to increased lipid peroxidation in insects. Here we report that rearing the greater wax moth, Galleria mellonella , on media supplemented with selected inhibitors of Eicosanoid biosynthesis throughout the larval, pupal and adult life led to major alterations in selected oxidative and antioxidative parameters of wax moth and its ectoparasitoid, Bracon hebetor . The highest dietary dexamethasone (Dex), esculetin (Esc) and phenidone (Phe) led to increased malondialdehyde (MDA) levels and to elevated catalase (CAT) and glutathione-S-transferase (GST) activities in all developmental stages of host larvae. Dietary Phe resulted in increased MDA levels, and CAT activity in G. mellonella adults by about 4-fold and about 2-fold, respectively. The Phe effect on GST activity in all stages of the wax moth was expressed in a dose-dependent manner, increased to 140 nmol/mg protein/min in larvae. MDA levels were increased by over 30-fold in adult wasps reared on Dex- and Esc-treated hosts. CAT and GST activities were increased in adult parasitoids reared on Esc-and Phe-treated hosts. GST activity of Dex-treated parasitoid larvae increased from about 4 to over 30 nmol/mg protein/min. Dietary Phe led to increased GST activity, by about 25-fold, in adult wasps. These data indicate that chronic inhibition of Eicosanoid biosynthesis leads to increased oxidative stress, strongly supporting our hypothesis. The significance of this work lies in understanding the roles of Eicosanoids in insect biology. Aside from other well-known Eicosanoids actions, we propose that Eicosanoids mediate reductions in oxidative stress.
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Eicosanoid ACTIONS IN INSECT IMMUNOLOGY
Insect Immunology, 2008Co-Authors: David Stanley, Jon S MillerAbstract:In this chapter we review Eicosanoid actions in insect immunity. Eicosanoids are oxygenated metabolites of arachidonic acid and two other C20 polyunsaturated fatty acids. Groups of Eicosanoids include prostaglandins, lipoxygenase products and epoxyeicosatrienoic acids. These compounds are most well studied in the context of biomedicine; however, we now know Eicosanoids act in insect immune defense reactions. These include the cellular mechanisms responsible for clearing bacterial infection from hemolymph circulation and in microaggregation and nodulation reactions. Eicosanoids also act in plasmatocyte spreading and hemocyte migration toward a chemical source. Various Eicosanoids act in insect defenses against bacteria, fungi, protozoan and parasitoid challenge. The most recent data indicate Eicosanoids act in insect defenses against viral infection. With a view to a coming generation of insect scientists, we lift up insect–virus interactions and mechanisms of Eicosanoid actions as two of the visible frontiers of insect immunology.
Xu Zhang - One of the best experts on this subject based on the ideXlab platform.
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Spectrum evaluation-assisted Eicosanoid metabolomics for global Eicosanoid profiling in human vascular endothelial cells.
Clinical and Experimental Pharmacology and Physiology, 2017Co-Authors: Hao Song, Ding Ai, Nan Yang, Xu ZhangAbstract:Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted Eicosanoid metabolomics is used to study the Eicosanoid profile in biological samples but only for Eicosanoids with available standards. To expand the coverage of Eicosanoids detected, we identified the Eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring- information dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied in this method, which was called Spectrum Evaluation-assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 Eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of Eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n-3 PUFA treatment. 26 putative Eicosanoids showed altered levels, despite no available standards. In general, n-3 PUFA treatment increased most of their own metabolites and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of Eicosanoids without standards. This article is protected by copyright. All rights reserved.
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Spectrum evaluation-assisted Eicosanoid metabolomics for global Eicosanoid profiling in human vascular endothelial cells.
Clinical and experimental pharmacology & physiology, 2017Co-Authors: Qiankun Bao, Nan Yang, Hao Song, Yajin Liu, Yi Zhu, Xu ZhangAbstract:Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted Eicosanoid metabolomics is used to study the Eicosanoid profile in biological samples but only for Eicosanoids with available standards. To expand the coverage of Eicosanoids detected, we identified the Eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring- information dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied in this method, which was called Spectrum Evaluation-assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 Eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of Eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n-3 PUFA treatment. 26 putative Eicosanoids showed altered levels, despite no available standards. In general, n-3 PUFA treatment increased most of their own metabolites and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of Eicosanoids without standards.
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systematic metabolomic analysis of Eicosanoids after omega 3 polyunsaturated fatty acid supplementation by a highly specific liquid chromatography tandem mass spectrometry based method
Journal of Proteome Research, 2015Co-Authors: Xu Zhang, Nan Yang, Ding AiAbstract:Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) have beneficial effects in many pathological processes, especially cardiovascular disease, and their protective Eicosanoid metabolites are thought to play important roles. However, how ω-3 PUFAs affect the Eicosanoid profile has not been elucidated comprehensively. Here, we systematically analyzed the Eicosanoid metabolites induced by ω-3 PUFA supplementation. We developed an LC–MS/MS-based method covering 32 arachidonic acid (ARA) metabolites and 37 ω-3 PUFA-derived products. The limits of detection for Eicosanoids were between 0.0625 and 1 pg and the detection specificity was optimized. We then quantified Eicosanoids in mouse and human plasma and mouse aorta samples after ω-3 PUFA supplementation. Levels of EPA hydroxyl products, 4-HDoHE, 17,18-EEQ, 17,18-DiHETE, TXB2, and LXA4 were significantly changed in both mouse samples, and those of 2-series PGs, EDPs and DHA hydroxyl products were changed in aorta samples. Correlation network analysis of mouse pl...
Edward A. Dennis - One of the best experts on this subject based on the ideXlab platform.
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Eicosanoid storm in infection and inflammation
Nature Reviews Immunology, 2015Co-Authors: Edward A. Dennis, Paul C. NorrisAbstract:Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique Eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti-inflammatory Eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here. Infection and injury cause controlled immune and inflammatory responses involving complex molecular signalling networks that lead to the production of bioactive lipid mediators. Eicosanoids are bioactive lipid mediators derived from oxygenated polyunsaturated fatty acids. Similar to cytokine signalling and inflammasome formation, Eicosanoid signalling has been viewed primarily as a pro-inflammatory component of innate immunity. Recent advances in lipidomics technologies have helped to elucidate unique Eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions that are a key component of the inflammatory response. Receptor activation initiated by Toll-like receptors (TLRs), purinergic receptors and other signalling pathways induced by infectious agents generates both pro-inflammatory and anti-inflammatory metabolites resulting in an Eicosanoid storm. Lipidomics has advanced our overall understanding of the inflammatory response and its therapeutic implications, and has suggested new pharmacological approaches. Eicosanoids are bioactive signalling lipids that regulate numerous homeostatic and inflammatory processes. Here, the authors review our current understanding of cellular Eicosanoid metabolism and the physiological functions of pro-inflammatory and pro-resolving Eicosanoids in infection and inflammation.
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Eicosanoid Storm in Infection and Inflammation
Nature Reviews Immunology, 2015Co-Authors: Edward A. Dennis, Paul C. NorrisAbstract:Eicosanoids are bioactive signalling lipids that regulate numerous homeostatic and inflammatory processes. Here, the authors review our current understanding of cellular Eicosanoid metabolism and the physiological functions of pro-inflammatory and pro-resolving Eicosanoids in infection and inflammation.
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Eicosanoid storm in infection and inflammation
Nature Reviews Immunology, 2015Co-Authors: Edward A. Dennis, Paul C. NorrisAbstract:Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique Eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti-inflammatory Eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here.
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targeted proteomics of the Eicosanoid biosynthetic pathway completes an integrated genomics proteomics metabolomics picture of cellular metabolism
Molecular & Cellular Proteomics, 2012Co-Authors: Eduard Sabido, Aaron M Armando, Edward A. Dennis, Oswald Quehenberger, Qin Shen, Chingyun Chang, Ishita Shah, Alexander Y Andreyev, Olga Vitek, Ruedi AebersoldAbstract:Eicosanoids constitute a diverse class of bioactive lipid mediators that are produced from arachidonic acid and play critical roles in cell signaling and inflammatory aspects of numerous diseases. We have previously quantified Eicosanoid metabolite production in RAW264.7 macrophage cells in response to Toll-like receptor 4 signaling and analyzed the levels of transcripts coding for the enzymes involved in the Eicosanoid metabolite biosynthetic pathways. We now report the quantification of changes in protein levels under similar experimental conditions in RAW264.7 macrophages by multiple reaction monitoring mass spectrometry, an accurate targeted protein quantification method. The data complete the first fully integrated genomic, proteomic, and metabolomic analysis of the Eicosanoid biochemical pathway.
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lipidomic analysis of dynamic Eicosanoid responses during the induction and resolution of lyme arthritis
Journal of Biological Chemistry, 2009Co-Authors: Victoria A Blaho, Matthew W Buczynski, Charles R Brown, Edward A. DennisAbstract:Eicosanoids and other bioactive lipid mediators are indispensable regulators of biological processes, as demonstrated by the numerous inflammatory diseases resulting from their dysregulation, including cancer, hyperalgesia, atherosclerosis, and arthritis. Despite their importance, a robust strategy comparable with gene or protein array technology for comprehensively analyzing the Eicosanoid metabolome has not been forthcoming. We have developed liquid chromatography-tandem mass spectrometry methodology that quantitatively and comprehensively analyzes the Eicosanoid metabolome and utilized this approach to characterize Eicosanoid production during experimental Lyme arthritis in mice infected with the bacterium Borrelia burgdorferi. Eicosanoids were extracted throughout infection from the joints of Lyme arthritis-resistant and -susceptible mice and subjected to lipidomic profiling. We identified temporal and quantitative differences between these mouse strains in the production of Eicosanoids, which correlated with differences in arthritis development. The Eicosanoid biosynthetic enzyme cyclooxygenase (COX)-2 has been implicated in the regulation of Lyme arthritis pathology, and subsequent lipidomic profiling of B. burgdorferi-infected COX-2(-/-) mice identified reductions not only in COX-2 products but, surprisingly, also significant off-target reductions in 5-lipoxygenase metabolites. Our results demonstrate the utility of a comprehensive lipidomic approach for identifying potential contributors to disease pathology and may facilitate the development of more precisely targeted treatment strategies.
Sony Shrestha - One of the best experts on this subject based on the ideXlab platform.
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Eicosanoids mediate prophenoloxidase release from oenocytoids in the beet armyworm spodoptera exigua
Insect Biochemistry and Molecular Biology, 2008Co-Authors: Sony ShresthaAbstract:Phenoloxidase (PO) plays a critical role in insect immune reactions especially to form melanotic encapsulation and phagocytosis by hemocytes. PO is an active form of prophenoloxidase (PPO) after proteolytic cleavage by serine proteinase(s). It has been suggested that Eicosanoids are implicated in PPO activation in the beet armyworm, Spodoptera exigua. However, it is not clear how Eicosanoids mediate the reaction cascade of PPO activation. This study analyzed the PPO activation mediated by Eicosanoids at both transcriptional and post-transcriptional levels. A cDNA encoding PPO (SePPO) was cloned from the hemocytes of S. exigua and its putative amino acid sequence shared homology with PPO-2 of other lepidopteran insects. Its expression was specific only to hemocytes and inducible in response to bacterial challenge. Eicosanoid biosynthesis inhibitors did not influence the gene expression of SePPO. Most SePPO proteins were located in a specific hemocyte type, oenocytoids, which were subjected to cell rupture to release the cellular contents in response to bacterial challenge. There was a significant negative correlation between PO activity and intact oenocytoid density. Interestingly, this cell rupture to release SePPO from oenocytoids was significantly inhibited in the larvae infected with the phospholipase A2-inhibiting bacterium, Xenorhabdus nematophila, which was resumed on addition of Eicosanoid biosynthesis precursor, arachidonic acid. Furthermore, oenocytoids exposed to Eicosanoid biosynthesis inhibitors such as dexamethasone and bromophenacyl bromide showed significant reduction in cell rupture. Prostaglandins, not lipoxygenase products appeared to be implicated in the cell rupture. These results indicate that Eicosanoids mediate SePPO activation only at the post-transcriptional level by inducing release of PPO from oenocytoids through cell rupture.
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Eicosanoids mediate prophenoloxidase release from oenocytoids in the beet armyworm spodoptera exigua
Insect Biochemistry and Molecular Biology, 2008Co-Authors: Sony ShresthaAbstract:Phenoloxidase (PO) plays a critical role in insect immune reactions especially to form melanotic encapsulation and phagocytosis by hemocytes. PO is an active form of prophenoloxidase (PPO) after proteolytic cleavage by serine proteinase(s). It has been suggested that Eicosanoids are implicated in PPO activation in the beet armyworm, Spodoptera exigua. However, it is not clear how Eicosanoids mediate the reaction cascade of PPO activation. This study analyzed the PPO activation mediated by Eicosanoids at both transcriptional and post-transcriptional levels. A cDNA encoding PPO (SePPO) was cloned from the hemocytes of S. exigua and its putative amino acid sequence shared homology with PPO-2 of other lepidopteran insects. Its expression was specific only to hemocytes and inducible in response to bacterial challenge. Eicosanoid biosynthesis inhibitors did not influence the gene expression of SePPO. Most SePPO proteins were located in a specific hemocyte type, oenocytoids, which were subjected to cell rupture to release the cellular contents in response to bacterial challenge. There was a significant negative correlation between PO activity and intact oenocytoid density. Interestingly, this cell rupture to release SePPO from oenocytoids was significantly inhibited in the larvae infected with the phospholipase A2-inhibiting bacterium, Xenorhabdus nematophila, which was resumed on addition of Eicosanoid biosynthesis precursor, arachidonic acid. Furthermore, oenocytoids exposed to Eicosanoid biosynthesis inhibitors such as dexamethasone and bromophenacyl bromide showed significant reduction in cell rupture. Prostaglandins, not lipoxygenase products appeared to be implicated in the cell rupture. These results indicate that Eicosanoids mediate SePPO activation only at the post-transcriptional level by inducing release of PPO from oenocytoids through cell rupture.
Ding Ai - One of the best experts on this subject based on the ideXlab platform.
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Spectrum evaluation-assisted Eicosanoid metabolomics for global Eicosanoid profiling in human vascular endothelial cells.
Clinical and Experimental Pharmacology and Physiology, 2017Co-Authors: Hao Song, Ding Ai, Nan Yang, Xu ZhangAbstract:Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted Eicosanoid metabolomics is used to study the Eicosanoid profile in biological samples but only for Eicosanoids with available standards. To expand the coverage of Eicosanoids detected, we identified the Eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring- information dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied in this method, which was called Spectrum Evaluation-assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 Eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of Eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n-3 PUFA treatment. 26 putative Eicosanoids showed altered levels, despite no available standards. In general, n-3 PUFA treatment increased most of their own metabolites and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of Eicosanoids without standards. This article is protected by copyright. All rights reserved.
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systematic metabolomic analysis of Eicosanoids after omega 3 polyunsaturated fatty acid supplementation by a highly specific liquid chromatography tandem mass spectrometry based method
Journal of Proteome Research, 2015Co-Authors: Xu Zhang, Nan Yang, Ding AiAbstract:Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) have beneficial effects in many pathological processes, especially cardiovascular disease, and their protective Eicosanoid metabolites are thought to play important roles. However, how ω-3 PUFAs affect the Eicosanoid profile has not been elucidated comprehensively. Here, we systematically analyzed the Eicosanoid metabolites induced by ω-3 PUFA supplementation. We developed an LC–MS/MS-based method covering 32 arachidonic acid (ARA) metabolites and 37 ω-3 PUFA-derived products. The limits of detection for Eicosanoids were between 0.0625 and 1 pg and the detection specificity was optimized. We then quantified Eicosanoids in mouse and human plasma and mouse aorta samples after ω-3 PUFA supplementation. Levels of EPA hydroxyl products, 4-HDoHE, 17,18-EEQ, 17,18-DiHETE, TXB2, and LXA4 were significantly changed in both mouse samples, and those of 2-series PGs, EDPs and DHA hydroxyl products were changed in aorta samples. Correlation network analysis of mouse pl...