Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4
| Autor: | Gregg Duester, Neal L. Weintraub, Bryce V. Plapp, Arthur A. Spector, Xiang Fang, T. Verugopal Raju, John R. Falck, Kristine B. Berst, Steven A. Moore, Xixuan H. Collins, Shawn D. Harmon, Terry L. Kaduce |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Telencephalon
Endothelium Cell Survival Metabolite Alcohol Dehydrogenase 4 Blotting Western Tritium Biochemistry Catalysis Muscle Smooth Vascular Cerebral circulation chemistry.chemical_compound Mice Hydroxyeicosatetraenoic Acids medicine Animals Enzyme Inhibitors Molecular Biology Cells Cultured Alcohol dehydrogenase biology Formamides Microcirculation Alcohol Dehydrogenase Cell Biology 20-Hydroxyeicosatetraenoic acid Lipids Recombinant Proteins Culture Media Kinetics medicine.anatomical_structure Eicosanoid ADH4 chemistry cardiovascular system biology.protein Oxidation-Reduction |
| Zdroj: | The Journal of biological chemistry. 280(39) |
| ISSN: | 0021-9258 |
| Popis: | 20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC) and endothelial (MEC) cultures obtained from mouse brain microvessels convert [3H]20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce this metabolite. The [3H]20-COOH-AA accumulated primarily in the culture medium, together with additional radiolabeled metabolites identified as the chain-shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N-Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction. Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA formation in the cerebral microvasculature. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|