5-Oxo-ETE and the OXE receptor.
5-Oxo-ETE is a product of the 5-lipoxygenase pathway that is formed by the oxidation of 5-HETE by 5-hydroxyeicosanoid dehydrogenase (5-HEDH). 5-HEDH is a microsomal NADP(+)-dependent enzyme that is highly selective for 5-HETE. 5-Oxo-ETE synthesis is regulated by intracellular NADP(+) levels and is dramatically increased under conditions that favor oxidation of NADPH to NADP(+) such as oxidative stress and the respiratory burst in phagocytic cells. 5-Oxo-ETE is a potent chemoattractant for eosinophils and has similar effects on neutrophils, basophils and monocytes. It elicits infiltration of eosinophils and, to a lesser extent, neutrophils into the skin after intradermal injection in humans. It also promotes the survival of tumor cells and has been shown to block the induction of apoptosis by 5-LO inhibitors. 5-Oxo-ETE acts by the G(i/o)-coupled OXE receptor, which was also known as TG1019, R527 and hGPCR48. Although the pathophysiological role of 5-oxo-ETE is not well understood, it may play important roles in asthma and allergic diseases, cancer, and cardiovascular disease. The availability of a selective antagonist would help to clarify the role of 5-oxo-ETE and may be of therapeutic benefit.
Grant
Gail E
GE
Meakins-Christie Laboratories, McGill University, QC, Canada.
Rokach
Joshua
J
Powell
William S
WS
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D002470:Cell Survival; D002630:Chemotactic Factors / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism; D018384:Oxidative Stress; D018055:Receptors, Eicosanoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D008024:Ligands; C504018:OXER1 protein, human; D018055:Receptors, Eicosanoid; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D000429:Alcohol Oxidoreductases; C099244:5-hydroxyeicosanoid dehydrogenase