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5-HETE

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William S. Powell – One of the best experts on this subject based on the ideXlab platform.

  • 5-oxo-ETE is a major oxidative stress-induced arachidonate metabolite in B lymphocytes.
    Free radical biology & medicine, 2011
    Co-Authors: Gail E. Grant, Joshua Rokach, Sylvie Gravel, J. Guay, Pranav Patel, Bruce Mazer, William S. Powell
    Abstract:

    Abstract B lymphocytes convert arachidonic acid (AA) to the 5-lipoxygenase products leukotriene B4 (LTB4) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) when subjected to oxidative stress. 5-HETE has little biological activity, but can be oxidized by a selective dehydrogenase in some cells to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemoattractant. We found that CESS cells, a B lymphocyte cell line, convert AA to 5-oxo-ETE and this is selectively stimulated by oxidative stress. In the presence of H2O2, 5-oxo-ETE is a major AA metabolite in these cells (5-oxo-ETE ≈ 5-HETE > LTB4). The cyclooxygenase product 12-hydroxy-5,8,10-heptadecatrienoic acid is also formed, but is not affected by H2O2. Diamide had effects similar to those of H2O2 and both substances had similar effects on human tonsillar B cells. H2O2 also stimulated 5-oxo-ETE formation from its direct precursor 5-HETE in tonsillar B and CESS cells, and this was inhibited by the glutathione reductase inhibitor carmustine. H2O2 concomitantly induced rapid increases in GSSG and NADP+ and reductions in GSH and NADPH. We conclude that oxidative stress stimulates 5-oxo-ETE synthesis in B lymphocytes by two mechanisms: activation of 5-lipoxygenase and increased oxidation of 5-HETE by NADP+-dependent 5-hydroxyeicosanoid dehydrogenase. B lymphocyte-derived 5-oxo-ETE could contribute to eosinophilic inflammation in asthma and other allergic diseases.

  • The design and synthesis of a 5-HETE affinity chromatography ligand for 5-hydroxyeicosanoid dehydrogenase
    Tetrahedron Letters, 2000
    Co-Authors: Subhash P. Khanapure, Goutam Saha, William S. Powell, Joshua Rokach
    Abstract:

    Abstract The first total synthesis of an ω-amino 5-HETE derivative 27 has been accomplished by a new counterclockwise strategy, in which C-1 is constructed first and C-20 last. The ω-amino 5-HETE derivative was transformed to an affinity chromatography ligand, the biotinylated 5-HETE 30. This affinity chromatography ligand is aimed at purifying the 5-hydroxyeicosanoid dehydrogenase enzyme, which is responsible for the conversion of 5-HETE to 5-oxo-ETE, a potent eosinophil chemotactic factor.

  • Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid by human monocytes and lymphocytes.
    Journal of leukocyte biology, 1996
    Co-Authors: Ying Zhang, Angela Styhler, William S. Powell
    Abstract:

    We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,1 1,14- eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,1 1 ,14-eicosatetraenoic acid (5-oxo- ETE), which is a potent stimulator of these cells. The objective of this study was to determine whether 5-oxo-ETE is also formed by monocytes and lympho- cytes. Human monocytes (74 ± 2% pure) and lym- phocytes (86 ± 1 % pure) were prepared by successive centrifugations of leukocytes over Ficoll-Paque and Percoll. Both cell types converted 5-HETE to a single major product, which was identified as 5-oxo- ETE. The formation of 5-oxo-ETE was stimulated about twofold by phorbol myristate acetate (PMA; 30 nM). Dehydrogenase activity in monocyte frac- tions did not appear to be due to platelet contamina- tion, since depletion of platelets did not reduce enzyme activity. The dehydrogenase was localized in membrane fractions from monocytes and required NADP+ as a cofactor. It was specific for eicosanoids containing a 5S-hydroxyl group followed by a 6-trans double bond. We also investigated the formation of 5-oxo-ETE from endogenous aracbidonic acid by monocytes. 5-Oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) were present in comparable amounts after incubation of these cells with A23187. PMA (EC50 -4 nM) stimulated the formation of 5-oxo-ETE and 5-HETE and, to a lesser extent, LTB4. Although monocytes released considerably less 5-HETE and LTB4 than neutrophils, they released comparable amounts of 5-oxo-ETE. Unlike neutrophils, mono- cytes did not convert any of these substances to detectable amounts of (li-oxidation products. Al- though lymphocytes were capable of converting 5- HETE to 5-oxo-ETE, they released little or no 5-lipoxygenase products in response to A23187. We conclude that monocytes have a high capacity to synthesize 5-oxo-ETE and that its formation is stimu- lated by activation of protein kinase C. J. Leukoc. Rio!. 59: 847-854; 1996.

Galina I. Myagkova – One of the best experts on this subject based on the ideXlab platform.

Igor Ivanov – One of the best experts on this subject based on the ideXlab platform.

  • A simple method for the preparation of (5Z,8Z,11Z,14Z)-16-hydroxyeicosa-5,8,11,14-tetraenoic acid enantiomers and the corresponding 14,15-dehydro analogues: role of the 16-hydroxy group for the lipoxygenase reaction.
    Bioorganic & medicinal chemistry, 2002
    Co-Authors: Igor Ivanov, Hartmut Kühn, Stepan G. Romanov, Nataliya V Groza, Santosh Nigam, Galina I. Myagkova
    Abstract:

    Abstract (5 Z ,8 Z ,11 Z ,13 E )-15-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) is not well oxygenated by arachidonate 15-lipoxygenases because of two structural reasons: (i) it contains a hydrophilic OH-group in close proximity to its methyl end and (ii) it lacks the bisallylic methylene at C 13 . We synthesized racemic (5 Z, 8 Z, 11 Z, 14 Z )-16-hydroxy-5,8,11,14-eicosatetraenoic acid (16-HETE) which still contains the bisallylic C 13 , separated the enantiomers reaching an optical purity of >99% and tested them as substrates for 5- and 15-lipoxygenases. Our synthetic pathway, which is based on stereospecific hydrogenation of a polyacetylenic precursor, yielded substantial amounts (30%) of 14,15-dehydro-16-HETE in addition to 16-HETE. When 16-HETE was tested as lipoxygenase substrate, we found that it is well oxygenated by the soybean 15-lipoxygenase and by the recombinant human 5-lipoxygenase. Analysis of the reaction products suggested an arachidonic acid-like alignment at the active site of the two enzymes. In contrast, the product pattern of 16-HETE methyl ester oxygenation by the soybean lipoxygenase (5-lipoxygenation) may be explained by an inverse head to tail substrate orientation.

Hartmut Kühn – One of the best experts on this subject based on the ideXlab platform.

Ying Zhang – One of the best experts on this subject based on the ideXlab platform.

  • Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid by human monocytes and lymphocytes.
    Journal of leukocyte biology, 1996
    Co-Authors: Ying Zhang, Angela Styhler, William S. Powell
    Abstract:

    We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,1 1,14- eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,1 1 ,14-eicosatetraenoic acid (5-oxo- ETE), which is a potent stimulator of these cells. The objective of this study was to determine whether 5-oxo-ETE is also formed by monocytes and lympho- cytes. Human monocytes (74 ± 2% pure) and lym- phocytes (86 ± 1 % pure) were prepared by successive centrifugations of leukocytes over Ficoll-Paque and Percoll. Both cell types converted 5-HETE to a single major product, which was identified as 5-oxo- ETE. The formation of 5-oxo-ETE was stimulated about twofold by phorbol myristate acetate (PMA; 30 nM). Dehydrogenase activity in monocyte frac- tions did not appear to be due to platelet contamina- tion, since depletion of platelets did not reduce enzyme activity. The dehydrogenase was localized in membrane fractions from monocytes and required NADP+ as a cofactor. It was specific for eicosanoids containing a 5S-hydroxyl group followed by a 6-trans double bond. We also investigated the formation of 5-oxo-ETE from endogenous aracbidonic acid by monocytes. 5-Oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) were present in comparable amounts after incubation of these cells with A23187. PMA (EC50 -4 nM) stimulated the formation of 5-oxo-ETE and 5-HETE and, to a lesser extent, LTB4. Although monocytes released considerably less 5-HETE and LTB4 than neutrophils, they released comparable amounts of 5-oxo-ETE. Unlike neutrophils, mono- cytes did not convert any of these substances to detectable amounts of (li-oxidation products. Al- though lymphocytes were capable of converting 5- HETE to 5-oxo-ETE, they released little or no 5-lipoxygenase products in response to A23187. We conclude that monocytes have a high capacity to synthesize 5-oxo-ETE and that its formation is stimu- lated by activation of protein kinase C. J. Leukoc. Rio!. 59: 847-854; 1996.