Identification and isolation of a membrane protein necessary for leukotriene production
- 1 January 1990
- journal article
- Published by Springer Nature in Nature
- Vol. 343 (6255) , 278-281
- https://doi.org/10.1038/343278a0
Abstract
Several inflammatory diseases, including asthma, arthritis and psoriasis are associated with the production of leukotrienes by neutrophils, mast cells and macrophages. The initial enzymatic step in the formation of leukotrienes is the oxidation of arachidonic acid by 5-lipoxygenase (5-LO) to leukotriene A4. Osteosarcoma cells transfected with 5-LO express active enzyme in broken cell preparations, but no leukotriene metabolites are produced by these cells when stimulated with the calcium ionophore A23187, indicating that an additional component is necessary for cellular 5-LO activity. A new class of indole leukotriene inhibitor has been described that inhibits the formation of cellular leukotrienes but has no direct inhibitory effect on soluble 5-LO activity. We have now used these potent agents to identify and isolate a novel membrane protein of relative molecular mass 18,000 which is necessary for cellular leukotriene synthesis.Keywords
This publication has 11 references indexed in Scilit:
- L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitorCanadian Journal of Physiology and Pharmacology, 1989
- Potential phospholipid source(s) of arachidonate used for the synthesis of leukotrienes by the human neutrophilBiochemical Journal, 1989
- Leukotrienes and Lipoxins: Structures, Biosynthesis, and Biological EffectsScience, 1987
- Characterization of leukotriene A4 synthase from murine mast cells: evidence for its identity to arachidonate 5-lipoxygenase.Proceedings of the National Academy of Sciences, 1986
- Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthase activities.Proceedings of the National Academy of Sciences, 1986
- Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid.Proceedings of the National Academy of Sciences, 1984
- Interactions between prostaglandins and leukotrienesBiochemical Pharmacology, 1984
- Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils.Proceedings of the National Academy of Sciences, 1983
- Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and InflammationScience, 1983
- The Glomerular Permeability Determined by Dextran Clearance Using Sephadex Gel FiltrationScandinavian Journal of Clinical and Laboratory Investigation, 1968