Synthesis of hydroxy fatty acids from linoleic acid by human blood platelets

Daret, Danièle; Blin, Patrick; Larrue, J

doi:10.1016/0090-6980(89)90083-x

Cited by 43 publications

(18 citation statements)

References 20 publications

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“…In contrast, we observed significant correlations between 4 LA‐derived oxylipids (13‐HODE, 9‐HODE, 12,13‐DiHOME, and 12,13‐EpOME) and collagen‐induced platelet aggregation post aspirin. Endothelial,16, 25, 52, 53 epidermal,26, 54 polymorphonuclear cells,27, 55 and platelets28, 56 convert LA into 13‐HODE and 9‐HODE. HODEs are active mediators in hemostasis, inflammation, and cancer invasion.…”

Section: Discussionmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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BackgroundWhile aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response.Methods and ResultsWe used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P=1.3×10−5), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen.ConclusionsTogether, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.

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Section: Discussionmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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“…LA was previously shown to be metabolized into 13-(S)-HODE, an oxidative metabolite, by 15-LOX (Daret et al, 1989;Wang et al, 1992), which is also a natural ligand for the β type of PPAR (Zuo et al, 2006). These findings suggested that the PPAR isoform selectivity of LA was promiscuous, and prompted us to investigate whether BKA (see the structure; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…LA (C18:2, Fig. 1) is a PUFA that acts as an activator of both the PPARα and γ isoforms (Kliewer et al, 1997;Zuo et al, 2006); however, it is also metabolized by 15-lipoxygenase (15-LOX), which leads to the production of a 13-(S)-hydroxyoctadecadienoic acid [13-(S)-HODE] (Daret et al, 1989;Wang et al, 1992) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform

et al. 2015

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-Bongkrekic acid (BKA), an antibiotic isolated from Pseudomonas cocovenans, is an inhibitory molecule of adenine nucleotide translocase. Since this translocase is a core component of the mitochondrial permeability transition pore (MPTP) formed by apoptotic stimuli, BKA has been used as a tool to abrogate apoptosis. However, the other biochemical properties of BKA have not yet been resolved. Although the definition of a fatty acid is a carboxylic acid (-COOH) with a long hydrocarbon chain (tail), when focused on the chemical structure of BKA, the molecule was revealed to be a branched unsaturated tricarboxylic acid that resembled the structure of polyunsaturated fatty acids (PUFAs). Peroxisome proliferator-activated receptors (PPARs) consist of a subfamily of three isoforms: α, β, and γ, the ligands of which include PUFAs. Using completely synthesized BKA together with simplified BKA derivatives (purity: > 98%), we herein demonstrated the utility of BKA as a selective activator of the human PPARγ isoform, which may not be associated with the anti-apoptotic nature of BKA. We also discussed the possible usefulness of BKA.

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“…To achieve this goal, the endogenous ligands that activate TRPV1 under physiological and pathophysiological conditions, such as inflammatory pain, need to be elucidated. 9‐hydroxyoctadecadienoic acid (9‐HODE) and 13‐HODE are oxidative metabolites of the essential fatty acid linoleic acid (LA) (Figure ), which can be generated via 15‐lipoxygenase (15‐LOX) in some tissues (Daret et al ., ; Baer et al ., ) and are known to activate TRPV1. 9‐HODE activates TRPV1 in transfected CHO cells, produces behavioural pain responses following spinal administration and is released following depolarization of the spinal cord in vitro (Patwardhan et al ., ).…”

Section: Introductionmentioning

confidence: 99%

The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms

Alsalem

Wong

Millns

et al. 2013

British J Pharmacology

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Background and Purpose The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9‐ and 13‐ hydroxyoctadecadienoic acid (HODE)] to TRPV1‐mediated noxious responses and inflammatory pain responses. Experimental Approach 9‐ and 13‐HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan‐inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9‐HODE‐ and 13‐HODE‐evoked responses, and the contribution of 15‐lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9‐ and 13‐HODE and 15‐lipoxygenase to inflammatory pain behaviour. Key Results 9‐HODE (35 ± 7 pmol g−1) and 13‐HODE (32 ± 6 pmol g−1) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9‐ and 13‐HODE were detected in DRGs and TRPV1 antagonist‐sensitive calcium responses evoked, which were blocked by the 15‐lipoxygenase inhibitor PD146176 and an anti‐13‐HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan‐inflamed hindpaw (P < 0.05), whereas levels of 9‐ and 13‐HODE were, however, decreased. Intraplantar co‐administration of anti‐9‐ and 13‐HODE antibodies and treatment with PD146176 significantly (P < 0.01) attenuated carrageenan‐induced hyperalgesia. Conclusions and Implications This study demonstrates that, although 9‐ and 13‐HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal.

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Synthesis of hydroxy fatty acids from linoleic acid by human blood platelets

Cited by 43 publications

References 20 publications

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform

The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms

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