Hepoxilin A3 synthase.

Abstract

Hepoxilins constitute a group of 12S-hydroperoxyeicosatetraenoic acid (12S-HpETE)-derived epoxy-hydroxy fatty acids that have been detected in various cell types and tissues. Although hepoxilin A3 (HXA3) exhibits a myriad of biological activities, its biosynthetic mechanism was not investigated in detail. Here we review the isolation, cloning, and characterization of a leukocyte-type 12S-lipoxygenase (12S-LOX) from rat insulinoma cells RINm5F, which exhibits an intrinsic hepoxilin A3 synthase activity. Confirmation for this observation was achieved by coimmunoprecipitation of HXA3 synthase activity with an anti-leukocyte 12S-LOX antibody, preparation of recombinant rat 12S-LOX enzyme from RINm5F cells, and assay of HXA3 synthase activity therein. Site-directed mutagenesis studies performed on rat 12S-LOX showed that 12-lipoxygenating enzyme species exhibit a strong HXA3 synthase activity that is impaired when the positional specificity of arachidonic acid is altered in favor of 15-lipoxygenation. Inasmuch as cellular glutathione peroxidases (cGPx and PHGPx) and HXA3 synthase compete for the same substrate 12S-HpETE, it can be proposed that the overall activity of glutathione peroxidases, representing the overall peroxide tone, finely tunes the rate of HXA3 formation.

• Authors: Santosh Nigam, Maria-Patapia Zafiriou
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 338 Issue 1 Pg. 161-8 (Dec 09 2005) ISSN: 0006-291X [Print] United States
• PMID: 16198304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Lipoxygenase Inhibitors
• Neoplasm Proteins
• 8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid
• Arachidonate 12-Lipoxygenase
• Arachidonate 15-Lipoxygenase
• Intramolecular Oxidoreductases
• hepoxilin synthase
• 8,11,14-Eicosatrienoic Acid

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, metabolism)
• Amino Acid Sequence
• Animals
• Arachidonate 12-Lipoxygenase (chemistry, genetics, metabolism)
• Arachidonate 15-Lipoxygenase (chemistry, metabolism)
• Cell Line, Tumor
• Intramolecular Oxidoreductases (antagonists & inhibitors, chemistry, genetics, metabolism)
• Lipoxygenase Inhibitors
• Molecular Sequence Data
• Neoplasm Proteins (antagonists & inhibitors, chemistry, genetics, metabolism)
• Rats
• Sequence Alignment