Significance and Immunoassay of 9- and 13-Hydroxyoctadecadienoic Acids

Spindler, Stephen A.; Clark, Kristi S.; Callewaert, Denis M.; Reddy, Ramesh G.

doi:10.1006/bbrc.1996.0033

Cited by 19 publications

(9 citation statements)

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“…Linoleic acid is the predominant PUFA in the diet and adipose tissue stores and can be metabolized by cyclooxygenase, lipoxygenase, and P450 enzymes (32). 13-HODE ϩ 9-HODE are monohydroxy lipoxygenation products and the most widely distributed of linoleic acid metabolites (17,32). The HODEs are secreted by a variety of cells including macrophages, endothelial cells, platelets, and smooth muscle cells, and exert biological and signaling activities as PPAR and GPR132 ligands (12,21,28,37).…”

Section: Discussionmentioning

confidence: 99%

Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling

Nieman

Shanely

Luo

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Nieman DC, Shanely RA, Luo B, Meaney MP, Dew DA, Pappan KL. Metabolomics approach to assessing plasma 13-and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling. Am J Physiol Regul Integr Comp Physiol 307: R68 -R74, 2014. First published April 23, 2014 doi:10.1152/ajpregu.00092.2014.-Bioactive oxidized linoleic acid metabolites (OXLAMs) include 13-and 9-hydroxy-octadecadienoic acid (13-HODE ϩ 9-HODE) and have been linked to oxidative stress, inflammation, and numerous pathological and physiological states. The purpose of this study was to measure changes in plasma 13-HODE ϩ 9-HODE following a 75-km cycling bout and identify potential linkages to linoleate metabolism and established biomarkers of oxidative stress (F2-isoprostanes) and inflammation (cytokines) using a metabolomics approach. Trained male cyclists (N ϭ 19, age 38.0 Ϯ 1.6 yr, wattsmax 304 Ϯ 10.5) engaged in a 75-km cycling time trial on their own bicycles using electromagnetically braked cycling ergometers (2.71 Ϯ 0.07 h). Blood samples were collected preexercise, immediately post-, 1.5 h post-, and 21 h postexercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, tumor necrosis factor-␣, monocyte chemoattractant protein-1, granulocyte colonystimulating factor), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). 13-HODE ϩ 9-HODE increased 3.1-fold and 1.7-fold immediately post-and 1.5 h postexercise (both P Ͻ 0.001) and returned to preexercise levels by 21-h postexercise. Post-75-km cycling plasma levels of 13-HODE ϩ 9-HODE were not significantly correlated with increases in plasma cytokines but were positively correlated with postexercise F 2-isoprostanes (r ϭ 0.75, P Ͻ 0.001), linoleate (r ϭ 0.54, P ϭ 0.016), arachidate (r ϭ 0.77, P Ͻ 0.001), 12,13-dihydroxy-9Z-octadecenoate (12,13-DiHOME) (r ϭ 0.60, P ϭ 0.006), dihomo-linolenate (r ϭ 0.57, P ϭ 0.011), and adrenate (r ϭ 0.56, P ϭ 0.013). These findings indicate that prolonged and intensive exercise caused a transient, 3.1-fold increase in the stable linoleic acid oxidation product 13-HODE ϩ 9-HODE and was related to increases in F 2-isoprostanes, linoleate, and fatty acids in the linoleate conversion pathway. These data support the use of 13-HODE ϩ 9-HODE as an oxidative stress biomarker in acute exercise investigations.

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Section: Discussionmentioning

confidence: 99%

Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling

Nieman

Shanely

Luo

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Determination of 13-HODE Levels by ELISA (19,20)-13-HODE was extracted from each sample at 4°C as follows. The solution was acidified to a pH of 3.5-4.0.…”

Section: Methodsmentioning

confidence: 99%

“…Electrophoretic Mobility Shift Assay (EMSA) (21,22)-The nuclear extractions from primary T cells were prepared as described (19). The sequences of the oligonucleotides (5Ј to 3Ј) used as probes were CACC-CCCATATTATTTTTCCAGCATT (NFAT) or AGTTGAGGGGACTTTC-CAGGC (NF-B).…”

Section: Methodsmentioning

confidence: 99%

Interleukin (IL)-4 Indirectly Suppresses IL-2 Production by Human T Lymphocytes via Peroxisome Proliferator-activated Receptor γ Activated by Macrophage-derived 12/15-Lipoxygenase Ligands

Yang¹,

Wang²,

Mihalic³

et al. 2002

Journal of Biological Chemistry

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The respective development of either T helper type 1 (Th1) or Th2 cells is believed to be mediated by the effects of cytokines acting directly on Th precursors (Thp). We have generated evidence for an indirect monocyte-dependent immunoregulatory pathway. Recently, interleukin (IL) 4 has been shown to produce "new" potential peroxisome proliferator-activated receptor ␥ (PPAR␥) ligands by inducing macrophage 12/ 15-lipoxygenase (12/15-LO). We have shown previously that the activated PPAR␥ is a profound inhibitor of IL-2 transcription in human T lymphocytes. It is hypothetically possible that IL-4 might indirectly affect IL-2 production by Thp cells via macrophage-derived PPAR␥ ligands. Using human monocytes and T lymphocytes from same donors, we have found that monocyte 12/15-LO products mediate the indirect inhibitory effect of IL-4 on anti-CD3-or phytohemagglutinin/ phorbol 12-myristate 13-acetate-stimulated IL-2 production by T lymphocytes. We further analyzed which major 12/15-LO metabolites contributed to the above inhibition. 13-Hydroxyoctadecadienoic acid (13-HODE), a 12/15-LO product, markedly blocked IL-2 production by human blood T lymphocytes, but not Jurkat T cells. Moreover, the IL-4-conditioned macrophage medium contained a sufficient amount of 13-HODE and anti-13-HODE antibody indeed neutralized the inhibitory effects of the IL-4-conditional medium on T-cell IL-2 production. Using human T lymphocytes and the PPAR␥-transfected Jurkat T cells, we demonstrated the specific inhibition by 13-HODE of the transcription factors NFAT (nuclear factor of activated T cells) and nuclear factor B, the IL-2 promoter reporter, and IL-2 production. However, 15-hydroxytetraenoic acid had little inhibitory effect. The potency of such inhibitory effects correlates well with the capability of the above metabolic lipids to activate PPAR␥. These data provide a mechanism whereby IL-4 may indirectly affect Thp function via PPAR␥ activated by macrophage products of the 12/15-LO pathway.

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“…S2). The specificity of these antibodies against the respective metabolites was previously established (12).…”

Section: Depolarization Of the Spinal Cord Leads To Increased Release Ofmentioning

confidence: 99%

“…The total 9-HODE content in the eluates was determined by using a commercially available ELISA kit (Oxford Biomedical Research). The method has been validated (12).…”

Section: Tg Cultures and Cho Cell Preparationmentioning

confidence: 99%

Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia

Patwardhan¹,

Scotland

Akopian³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

198

191

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Transient receptor potential vanilloid 1 (TRPV1) plays a major role in hyperalgesia and allodynia and is expressed both in the peripheral and central nervous systems (CNS). However, few studies have evaluated mechanisms by which CNS TRPV1 mediates hyperalgesia and allodynia after injury. We hypothesized that activation of spinal cord systems releases endogenous TRPV1 agonists that evoke the development of mechanical allodynia by this receptor. Using in vitro superfusion, the depolarization of spinal cord triggered the release of oxidized linoleic acid metabolites, such as 9-hydroxyoctadecadienoic acid (9-HODE) that potently activated spinal TRPV1, leading to the development of mechanical allodynia. Subsequent calcium imaging and electrophysiology studies demonstrated that synthetic oxidized linoleic acid metabolites, including 9-HODE, 13-HODE, and 9 and 13-oxoODE, comprise a family of endogenous TRPV1 agonists. In vivo studies demonstrated that intrathecal application of these oxidized linoleic acid metabolites rapidly evokes mechanical allodynia. Finally, intrathecal neutralization of 9-and 13-HODE by antibodies blocks CFA-evoked mechanical allodynia. These data collectively reveal a mechanism by which an endogenous family of lipids activates TRPV1 in the spinal cord, leading to the development of inflammatory hyperalgesia. These findings may integrate many pain disorders and provide an approach for developing analgesic drugs.inflammation ͉ pain T ransient receptor potential vanilloid 1 (TRPV1) plays a pivotal role in many pain models, leading to the development of hyperalgesia and/or allodynia (1-2). TRPV1 is expressed in the peripheral as well as central nervous systems (CNS) including several areas involved in nociceptive transmission (3). Numerous studies have demonstrated that peripheral TRPV1 is activated by noxious heat and protons and is regulated by endogenous ligands (2), contributing to peripheral mechanisms of heat hyperalgesia (4). However, TRPV1 is also expressed in the CNS, where comparatively little is known about the role of this receptor in mediating central pain mechanisms.Recent studies have used TRPV1 antagonists to evaluate the role of CNS TRPV1 in inflammatory hyperalgesia. Interestingly, the systemic/spinal administration of TRPV1 antagonists blocks inflammation-induced heat hyperalgesia, as well as mechanical allodynia (5-6). These findings were unexpected since TRPV1 is not activated by mechanical stimuli, suggesting that spinal TRPV1 activation leads to central sensitization to both thermal and mechanical stimuli (7-8). Based upon these observations, we hypothesized that the afferent barrage resulting from peripheral tissue injury leads to generation of endogenous TRPV1 ligands in the spinal cord that activate TRPV1 in the CNS resulting in central sensitization. Results Depolarization of Spinal Cord Results in the Release of EndogenousTRPV1 Ligands. To evaluate the hypothesis that endogenous TRPV1 agonists are released from spinal cord neurons, freshly isolated male rat spinal cords w...

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Significance and Immunoassay of 9- and 13-Hydroxyoctadecadienoic Acids

Cited by 19 publications

References 0 publications

Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling

Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling

Interleukin (IL)-4 Indirectly Suppresses IL-2 Production by Human T Lymphocytes via Peroxisome Proliferator-activated Receptor γ Activated by Macrophage-derived 12/15-Lipoxygenase Ligands

Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia

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