5-Oxo-ETE and the OXE receptor

Prostaglandins Other Lipid Mediat. 2009 Sep;89(3-4):98-104. doi: 10.1016/j.prostaglandins.2009.05.002. Epub 2009 May 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Arachidonic Acids / metabolism*
  • Asthma / metabolism
  • Cardiovascular Diseases / metabolism
  • Cell Survival
  • Chemotactic Factors / metabolism
  • Humans
  • Ligands
  • Neoplasms / metabolism
  • Oxidative Stress
  • Receptors, Eicosanoid / antagonists & inhibitors
  • Receptors, Eicosanoid / genetics
  • Receptors, Eicosanoid / metabolism*
  • Signal Transduction

Substances

  • Arachidonic Acids
  • Chemotactic Factors
  • Ligands
  • OXER1 protein, human
  • Receptors, Eicosanoid
  • 5-oxo-6,8,11,14-eicosatetraenoic acid
  • Alcohol Oxidoreductases
  • 5-hydroxyeicosanoid dehydrogenase