5-Oxo-ETE is a major oxidative stress-induced arachidonate metabolite in B lymphocytes
| Autor: | Bruce Mazer, J. Guay, Pranav Patel, William S. Powell, Gail E. Grant, Sylvie Gravel, Joshua Rokach |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Leukotriene B4
Lymphocyte Glutathione reductase medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Physiology (medical) medicine Humans Calcimycin 030304 developmental biology B-Lymphocytes 0303 health sciences Arachidonate 5-Lipoxygenase Arachidonic Acid biology Hydrogen Peroxide Glutathione Eosinophil Oxidative Stress medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Arachidonate 5-lipoxygenase biology.protein Arachidonic acid Oxidation-Reduction Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine. 50:1297-1304 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2011.02.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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