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Charles N Serhan - One of the best experts on this subject based on the ideXlab platform.
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Presentation_1_Protectins PCTR1 and PD1 Reduce Viral Load and Lung Inflammation During Respiratory Syncytial Virus Infection in Mice.pdf
'Frontiers Media SA', 2021Co-Authors: Katherine H. Walker, Charles N Serhan, Nandini Krishnamoorthy, Thayse R. Brüggemann, Ashley E. Shay, Bruce D. LevyAbstract:Viral pneumonias are a major cause of morbidity and mortality, owing in part to dysregulated excessive lung inflammation, and therapies to modulate host responses to viral lung injury are urgently needed. Protectin conjugates in tissue regeneration 1 (PCTR1) and Protectin D1 (PD1) are specialized pro-resolving mediators (SPMs) whose roles in viral pneumonia are of interest. In a mouse model of Respiratory Syncytial Virus (RSV) pneumonia, intranasal PCTR1 and PD1 each decreased RSV genomic viral load in lung tissue when given after RSV infection. Concurrent with enhanced viral clearance, PCTR1 administration post-infection, decreased eosinophils, neutrophils, and NK cells, including NKG2D+ activated NK cells, in the lung. Intranasal PD1 administration post-infection decreased lung eosinophils and Il-13 expression. PCTR1 increased lung expression of cathelicidin anti-microbial peptide and decreased interferon-gamma production by lung CD4+ T cells. PCTR1 and PD1 each increased interferon-lambda expression in human bronchial epithelial cells in vitro and attenuated RSV-induced suppression of interferon-lambda in mouse lung in vivo. Liquid chromatography coupled with tandem mass spectrometry of RSV-infected and untreated mouse lungs demonstrated endogenous PCTR1 and PD1 that decreased early in the time course while cysteinyl-leukotrienes (cys-LTs) increased during early infection. As RSV infection resolved, PCTR1 and PD1 increased and cys-LTs decreased to pre-infection levels. Together, these results indicate that PCTR1 and PD1 are each regulated during RSV pneumonia, with overlapping and distinct mechanisms for PCTR1 and PD1 during the resolution of viral infection and its associated inflammation.
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Protectins PCTR1 and PD1 Reduce Viral Load and Lung Inflammation During Respiratory Syncytial Virus Infection in Mice
'Frontiers Media SA', 2021Co-Authors: Katherine H. Walker, Charles N Serhan, Nandini Krishnamoorthy, Thayse R. Brüggemann, Ashley E. Shay, Bruce D. LevyAbstract:Viral pneumonias are a major cause of morbidity and mortality, owing in part to dysregulated excessive lung inflammation, and therapies to modulate host responses to viral lung injury are urgently needed. Protectin conjugates in tissue regeneration 1 (PCTR1) and Protectin D1 (PD1) are specialized pro-resolving mediators (SPMs) whose roles in viral pneumonia are of interest. In a mouse model of Respiratory Syncytial Virus (RSV) pneumonia, intranasal PCTR1 and PD1 each decreased RSV genomic viral load in lung tissue when given after RSV infection. Concurrent with enhanced viral clearance, PCTR1 administration post-infection, decreased eosinophils, neutrophils, and NK cells, including NKG2D+ activated NK cells, in the lung. Intranasal PD1 administration post-infection decreased lung eosinophils and Il-13 expression. PCTR1 increased lung expression of cathelicidin anti-microbial peptide and decreased interferon-gamma production by lung CD4+ T cells. PCTR1 and PD1 each increased interferon-lambda expression in human bronchial epithelial cells in vitro and attenuated RSV-induced suppression of interferon-lambda in mouse lung in vivo. Liquid chromatography coupled with tandem mass spectrometry of RSV-infected and untreated mouse lungs demonstrated endogenous PCTR1 and PD1 that decreased early in the time course while cysteinyl-leukotrienes (cys-LTs) increased during early infection. As RSV infection resolved, PCTR1 and PD1 increased and cys-LTs decreased to pre-infection levels. Together, these results indicate that PCTR1 and PD1 are each regulated during RSV pneumonia, with overlapping and distinct mechanisms for PCTR1 and PD1 during the resolution of viral infection and its associated inflammation
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Synthesis and Anti-inflammatory and Pro-resolving Activities of 22- OH-PD1, a Monohydroxylated Metabolite of Protectin D1
2016Co-Authors: Jørn E. Tungen, Charles N Serhan, Jesmond Dalli, Romain A. Colas, Marius Aursnes, Anders Vik, Sesquile Ramon, Trond V. HansenAbstract:ABSTRACT: Protectin D1 (PD1 (3)), a C22-dihydroxylated polyunsaturated fatty acid biosynthesized from all-Z-docosahexaenoic acid, belongs to the new family of endogenous mediators referred to as specialized pro-resolving lipid mediators. PD1 (3) is a natural product that displays potent anti-inflammatory properties together with pro-resolving actions including inhibition of polymorphonuclear leukocyte (PMN) infiltration and promotion of macrophage phagocytosis and efferocytosis. Given its potent endogenous actions, this compound has entered several clinical development programs. Little has been reported on the metabolism of PD1 (3). The synthesis and biological evaluations of the ω-22 monohydroxylated metabolite of PD1 (3), named herein 22-OH-PD1 (6), are presented. LC-MS/MS data of the free acid 6, obtained from hydrolysis of the synthetic methyl ester 7, matched data for the endogenously produced 22-OH-PD1 (6). Compound 6 exhibited potent pro-resolving actions by inhibiting PMN chemotaxis in vivo and in vitro comparable to its precursor PD1 (3) and decreased pro-inflammatory mediator levels in inflammatory exudates. The results reported herein provide new knowledge of the metabolism of the Protectin class of specialized pro-resolving mediators. Several naturally occurring chemical mediators have beenidentified that have the capacity to initiate, modulate, and reduce acute inflammation as well as stimulate resolution.1,2 Recent efforts have established that the return to homeostasis, i.e., catabasis,3 is mediated by active biosynthesis an
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The Docosatriene Protectin D1 Is Produced by TH2
2015Co-Authors: Katherine H. Gotlinger, Charles N SerhanAbstract:Docosahexaenoic acid, a major -3 fatty acid in human brain, synapses, retina, andotherneural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatogra-phy-tandemmass spectrometry, that (10,17S)-docosatriene/neuro-Protectin D1, now termed Protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor and interferon- secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflamma-tory roles for PD1 in regulating events associated with inflamma-tion and resolution. Chemical mediators and autacoids, such as the local-acting lipi
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Protectins and Maresins: New Pro-Resolving Families of Mediators in Acute Inflammation and Resolution Bioactive Metabolome
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2015Co-Authors: Charles N Serhan, Jesmond Dalli, Romain A. Colas, Jeremy W. Winkler, Nan ChiangAbstract:Abstract Acute inflammatory responses are protective, yet without timely resolution can lead to chronic inflammation and organ fibrosis. A systems approach to investigate self-limited (self-resolving) inflammatory exudates in mice and structural elucidation uncovered novel resolution phase mediators in vivo that stimulate endogenous resolution mechanisms in inflammation. Resolving inflammatory exudates and human leukocytes utilize DHA and other n− 3 EFA to produce three structurally distinct families of potent di- and trihydroxy-containing products, with several stereospecific potent mediators in each family. Given their potent and stereoselective picogram actions, specific members of these new families of mediators from the DHA metabolome were named D-series resolvins (Resolvin D1 to Resolvin D6), Protectins (including Protectin D1 –neuroProtectin D1), and maresins (MaR1 and MaR2). In this review, we focus on a) biosynthesis of Protectins and maresins as anti-inflammatory–pro-resolving mediators; b) their complete stereochemical assignments and actions in vivo in disease models. Each pathway involves the biosynthesis of epoxide-containing intermediates produced from hydroperoxy-containing precursors from human leukocytes and within exudates. Also, aspirin triggers an endogenous DHA metabolome that biosynthesizes potent products in inflammatory exudates and human leukocytes, namely aspirin-triggered NeuroProtectin D1/Protectin D1 [AT-(NPD1/PD1)]. Identification and structural elucidation of these new families of bioactive mediators in resolution has opened the possibility of diverse patho-physiologic actions in several processes including infection, inflammatory pain, tissue regeneration, neuroprotection-neurodegenerative disorders, wound healing, and others. This article is part of a Special Issue entitled “Oxygenated metabolism of PUFA: analysis and biological relevance”.
Rong Yang - One of the best experts on this subject based on the ideXlab platform.
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stereocontrolled total synthesis of neuroProtectin D1 Protectin D1 and its aspirin triggered stereoisomer
Tetrahedron Letters, 2012Co-Authors: Nicos A Petasis, Rong Yang, Jeremy W. Winkler, Min Zhu, Jasim Uddin, Nicolas G Bazan, Charles N SerhanAbstract:NeuroProtectin D1 / Protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne precursors, while the conjugated E,E,Z triene was introduced at the end, in order to minimize Z/E isomerization. The same strategy, was also employed for the total synthesis of aspirin-triggered neuroProtectin D1 / Protectin D1 having the 17(R)-stereochemistry. Synthetic compounds obtained with the reported method were matched with endogenously derived materials, and helped establish their complete stereochemistry.
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metabolomics lipidomics of eicosanoids and docosanoids generated by phagocytes
Current protocols in immunology, 2011Co-Authors: Rong Yang, Nan Chiang, Sungwhan F OhAbstract:Lipid mediators derived from essential fatty acids, such as arachidonic acid, play important roles in physiologic and pathophysiologic processes. Prostaglandins, thromboxane, and leukotrienes are well-known eicosanoids that play critical roles in hemodynamics and inflammation. New families of mediators were recently uncovered that constitute a new genus stimulating resolution of acute inflammation, and are organ-protective. These include the resolvins (E-series and D-series), Protectins (neuroProtectin D1/Protectin D1), and maresins biosynthesized from omega-3 essential fatty acids. Phagocytes play major roles in tissue homeostasis and have a high capacity to produce these mediators, which depend on their tissue and state of activation. It is important to select appropriate methods for identifying target mediators and pathway biomarkers. In this unit, we review state-of-the-art approaches to identify and profile eicosanoid and docosanoid pathways, including specialized pro-resolving mediators resolvins, Protectins, and maresins, in relation to their biosynthesis and inactivation by neutrophils and macrophages.
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maresins novel macrophage mediators with potent antiinflammatory and proresolving actions
Journal of Experimental Medicine, 2009Co-Authors: Rong Yang, Kimberly Martinod, Kie Kasuga, Padmini S Pillai, Timothy F Porter, Sungwhan F Oh, Matthew SpiteAbstract:The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and Protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated MΦs converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and Protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MΦ mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense.
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resolvin D1 Protectin D1 and related docosahexaenoic acid derived products analysis via electrospray low energy tandem mass spectrometry based on spectra and fragmentation mechanisms
Journal of the American Society for Mass Spectrometry, 2007Co-Authors: Katherine H. Gotlinger, Rong Yang, Nicos A Petasis, Song Hong, Charles N SerhanAbstract:Resolvin D1 (RvD1) and Protectin D1 (NeuroProtectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm − 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or 1H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc − H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissue.
Song Hong - One of the best experts on this subject based on the ideXlab platform.
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neuroProtectin Protectin D1 endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes
American Journal of Physiology-cell Physiology, 2014Co-Authors: Song Hong, Charles N Serhan, Haibin Tian, James Monroe Laborde, Filipe A Muhale, Quansheng Wang, Bhagwat V Alapure, Nicolas G BazanAbstract:Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroProtectin/Protectin D1 (NPD1/PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13...
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resolvin D1 Protectin D1 and related docosahexaenoic acid derived products analysis via electrospray low energy tandem mass spectrometry based on spectra and fragmentation mechanisms
Journal of the American Society for Mass Spectrometry, 2007Co-Authors: Katherine H. Gotlinger, Rong Yang, Nicos A Petasis, Song Hong, Charles N SerhanAbstract:Resolvin D1 (RvD1) and Protectin D1 (NeuroProtectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm − 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or 1H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc − H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissue.
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the docosatriene Protectin D1 is produced by th2 skewing and promotes human t cell apoptosis via lipid raft clustering
Journal of Biological Chemistry, 2005Co-Authors: Amiram Ariel, Gabrielle Fredman, Katherine H. Gotlinger, Song Hong, Wei Wang, Wangxian Tang, Charles N SerhanAbstract:Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroProtectin D1, now termed Protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor alpha and interferon-gamma secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.
Katherine H. Gotlinger - One of the best experts on this subject based on the ideXlab platform.
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The Docosatriene Protectin D1 Is Produced by TH2
2015Co-Authors: Katherine H. Gotlinger, Charles N SerhanAbstract:Docosahexaenoic acid, a major -3 fatty acid in human brain, synapses, retina, andotherneural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatogra-phy-tandemmass spectrometry, that (10,17S)-docosatriene/neuro-Protectin D1, now termed Protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor and interferon- secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflamma-tory roles for PD1 in regulating events associated with inflamma-tion and resolution. Chemical mediators and autacoids, such as the local-acting lipi
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identification of inflammatory and proresolving lipid mediators in bone marrow and their lipidomic profiles with ovariectomy and omega 3 intake
American Journal of Hematology, 2008Co-Authors: Raewyn C Poulsen, Charles N Serhan, Katherine H. Gotlinger, Marlena C KrugerAbstract:Newly described lipoxygenase (LOX)-generated lipid mediators, that is, resolvins and Protectins as well as lipoxins, are both anti-inflammatory and proresolving. We aimed to determine whether these lipid mediators are present in bone marrow and whether their lipidomic profiles are altered following ovariectomy or dietary supplementation with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) ethyl esters. Female rats were ovariectomised or sham-operated. Shams and one ovariectomised group received a diet devoid of omega-3 long-chain polyunsaturated fatty acids. The remaining ovariectomised rats received either 0.5 g EPA or DHA ethyl ester/kg body weight/day for 4 months. Bone marrow was analyzed using both GC to determine fatty acid composition and mediator lipidomics by LC/MS/MS profiling for the presence of LOX-pathway lipid mediators derived from arachidonic acid (AA), EPA, and DHA. LOX-derived products including lipoxins, resolvin D1, resolvin E1, and Protectin D1 were identified in bone marrow by the presence of diagnostic ions in their corresponding MS-MS spectra. The proportion of AA relative to DHA and of AA-derived relative to DHA-derived mediators in bone marrow was higher in ovariectomised compared to sham-operated rats. DHA or EPA ethyl ester supplementation increased the percentage of DHA and EPA in bone marrow and increased the proportion of LOX mediators biosynthesized from DHA or EPA, respectively. Given the potent bioactivities of the lipoxins, resolvins, and Protectins, the presence and changes in profile postovariectomy and with EPA and DHA ethyl ester supplementation may be of interest in bone marrow function and as a potential source of these mediators in vivo.
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resolvin D1 Protectin D1 and related docosahexaenoic acid derived products analysis via electrospray low energy tandem mass spectrometry based on spectra and fragmentation mechanisms
Journal of the American Society for Mass Spectrometry, 2007Co-Authors: Katherine H. Gotlinger, Rong Yang, Nicos A Petasis, Song Hong, Charles N SerhanAbstract:Resolvin D1 (RvD1) and Protectin D1 (NeuroProtectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm − 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or 1H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc − H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissue.
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the docosatriene Protectin D1 is produced by th2 skewing and promotes human t cell apoptosis via lipid raft clustering
Journal of Biological Chemistry, 2005Co-Authors: Amiram Ariel, Gabrielle Fredman, Katherine H. Gotlinger, Song Hong, Wei Wang, Wangxian Tang, Charles N SerhanAbstract:Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroProtectin D1, now termed Protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor alpha and interferon-gamma secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.
Nicos A Petasis - One of the best experts on this subject based on the ideXlab platform.
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stereocontrolled total synthesis of neuroProtectin D1 Protectin D1 and its aspirin triggered stereoisomer
Tetrahedron Letters, 2012Co-Authors: Nicos A Petasis, Rong Yang, Jeremy W. Winkler, Min Zhu, Jasim Uddin, Nicolas G Bazan, Charles N SerhanAbstract:NeuroProtectin D1 / Protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne precursors, while the conjugated E,E,Z triene was introduced at the end, in order to minimize Z/E isomerization. The same strategy, was also employed for the total synthesis of aspirin-triggered neuroProtectin D1 / Protectin D1 having the 17(R)-stereochemistry. Synthetic compounds obtained with the reported method were matched with endogenously derived materials, and helped establish their complete stereochemistry.
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resolvin D1 Protectin D1 and related docosahexaenoic acid derived products analysis via electrospray low energy tandem mass spectrometry based on spectra and fragmentation mechanisms
Journal of the American Society for Mass Spectrometry, 2007Co-Authors: Katherine H. Gotlinger, Rong Yang, Nicos A Petasis, Song Hong, Charles N SerhanAbstract:Resolvin D1 (RvD1) and Protectin D1 (NeuroProtectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm − 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or 1H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc − H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissue.
