Identification and Structure Determination of Novel Anti-inflammatory Mediator Resolvin E3, 17,18-Dihydroxyeicosapentaenoic Acid

Isobe, Yosuke; Arita, Makoto; Matsueda, Shinnosuke; Iwamoto, Ryo; Fujihara, Takuji; Nakanishi, Hiroki; Taguchi, Ryo; Masuda, Koji; Sasaki, Katsuhiko; Urabe, Daisuke; Inoue, M.; Arai, Hiroyuki

doi:10.1074/jbc.m112.340612

Cited by 207 publications

(186 citation statements)

References 27 publications

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“…There are few data attesting to their formation in humans based on rigorous mass spectrometric methodology. Most clinical investigations reporting the formation of SPMs rely on immunoassays ( 21 ) or MS without synthetic internal standards structurally similar to the SPMs under investigation (22)(23)(24)(25)(26)(27)(29)(30)(31)(32), often in ex vivo stimulated systems ( 17,(33)(34)(35)(36).…”

Section: Blood (Rbc Membranes) For the Study High Doses Of Lovaza Fishmentioning

confidence: 99%

Bioactive products formed in humans from fish oils

Skarke

Alamuddin

Lawson

et al. 2015

Journal of Lipid Research

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The clinical cardiovascular utility of a diet rich in fi sh oils, particularly EPA and DHA, has been debated over the past 50 years ( 1-3 ). Large clinical outcome trials, such as the open-labeled GISSI-Prevenzione ( 4 ) or JELIS ( 5 ) studies, supported the notion that fi sh oil supplements confer therapeutic benefi t on patients with cardiovascular disease. However, an overview analysis of results of more than 50 randomized controlled trials and cohort studies addressing this question yielded equivocal results ( 6, 7 ). Consequently, the adoption of the dietary interventions with fi sh oil into clinical guidelines has been limited ( 8 ). Fish oil supplementation does infl uence a series of cardiovascular biomarkers: it decreases blood levels of triglycerides in patients with hypertriglyceridemia, an effect primarily driven by lowering the production of triglycerides from nonesterifi ed fatty acids ( 9 ); high doses reduce blood pressure in patients with essential hypertension ( 10, 11 ) and modestly inhibit indices of platelet activation ( 12 ). The mechanisms involved are unclear, but may involve a shift in formation of enzymatic and free radical-catalyzed prostanoids, refl ecting utilization of EPA and DHA rather than arachidonic acid (AA) as a substrate. It has been speculated also that cardiovascular benefi t might derive, in part, from anti-infl ammatory actions of fi sh oils: families of bioactive lipids which favor resolution of infl ammation have been suggested to be of particular importance ( 13 ). Synthetic versions of such specialized pro-resolving mediators (SPMs), products of transcellular metabolism of fi sh oils, exert anti-infl ammatory effects in vitro and when administered in vivo in several animal models ( 14-17 ). Quantities Abstract Resolvins, maresins, and protectins can be formed from fi sh oils. These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of infl ammation. Synthetic versions of such SPMs exert anti-infl ammatory effects in vitro and when administered to animal models. However, their importance as endogenous products formed in suffi cient amounts to exert anti-infl ammatory actions in vivo remains speculative. We biased our ability to detect SPMs formed in healthy volunteers by supplementing fi sh oil in doses shown previously to infl uence blood pressure and platelet aggregation under placebo-controlled conditions. Additionally, we sought to determine the relative formation of SPMs during an acute infl ammatory response and its resolution, evoked in healthy volunteers by bacterial lipopolysaccharide (LPS). Bioactive lipids, enzymatic epoxyeicosatrienoic acids (EETs), and free radical-catalyzed prostanoids [isoprostanes (iPs)] formed from arachidonic acid and the fi sh oils, served as comparators. Despite the clear shift from -6 to -3 EETs and iPs, we failed to detect a consistent signal, in most cases, of SPM formation in urine or plasma in response to fi sh oil, and in all cases in response to LPS on a background of fi sh oil. Our results que...

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Section: Blood (Rbc Membranes) For the Study High Doses Of Lovaza Fishmentioning

confidence: 99%

Bioactive products formed in humans from fish oils

Skarke

Alamuddin

Lawson

et al. 2015

Journal of Lipid Research

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show abstract

“…4B , 12-HETE). Recently, Isobe et al reported that HEK293 cells produced a signifi cant amount of 12-HETE after incubation with 10 µM arachidonic acid ( 25 ), suggesting that excess arachidonic acid is converted to 12-HETE in HEK293 cells, possibly by endogenous 12-lipoxygenase. Figure 4 suggests that TxAS is dispensable for 12-HHT production but indispensable for TxB 2 production in COX-1-expressing cells.…”

Section: Production Of 12-hht and Txb 2 In Human Plateletsmentioning

confidence: 99%

Thromboxane A synthase-independent production of 12-hydroxyheptadecatrienoic acid, a BLT2 ligand

Matsunobu

Okuno

Yokoyama

et al. 2013

Journal of Lipid Research

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“…RvE3 was biosynthesized from EPA by P450 or aspirin-acetylated cyclooxygenase-2, followed by 15-lipoxygenase activity. 25 TNF-α stimulation had no effects on lipoxygenase expression, and EPA-rich rHDL induced RvE3 production, suggesting that RvE3 production is directly reflected by the amount of EPA. Surprisingly, the HDL structure appeared to be necessary for the efficient conversion of EPA-PC to 18-HEPE and RvE3 by endothelial cells.…”

Section: Preparation and Characterization Of Rhdlmentioning

confidence: 88%