Hepoxilin A3 synthase
- PMID: 16198304
- DOI: 10.1016/j.bbrc.2005.09.065
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.
Similar articles
-
The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity.J Biol Chem. 2004 Jul 9;279(28):29023-30. doi: 10.1074/jbc.M307576200. Epub 2004 May 3. J Biol Chem. 2004. PMID: 15123652
-
Structure, biochemistry and biology of hepoxilins: an update.FEBS J. 2007 Jul;274(14):3503-3512. doi: 10.1111/j.1742-4658.2007.05910.x. Epub 2007 Jul 2. FEBS J. 2007. PMID: 17608719 Review.
-
Biological role of hepoxilins: upregulation of phospholipid hydroperoxide glutathione peroxidase as a cellular response to oxidative stress?Prostaglandins Leukot Essent Fatty Acids. 2007 Oct-Nov;77(3-4):209-15. doi: 10.1016/j.plefa.2007.08.007. Epub 2007 Nov 7. Prostaglandins Leukot Essent Fatty Acids. 2007. PMID: 17997296
-
Biosynthesis of hepoxilins: evidence for the presence of a hepoxilin synthase activity in rat insulinoma cells.FEBS Lett. 2003 Mar 13;538(1-3):107-12. doi: 10.1016/s0014-5793(03)00151-0. FEBS Lett. 2003. PMID: 12633862
-
The hepoxilins and some analogues: a review of their biology.Br J Pharmacol. 2009 Oct;158(4):972-81. doi: 10.1111/j.1476-5381.2009.00168.x. Epub 2009 Apr 30. Br J Pharmacol. 2009. PMID: 19422397 Free PMC article. Review.
Cited by
-
ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.PLoS One. 2013 Jun 24;8(6):e67117. doi: 10.1371/journal.pone.0067117. Print 2013. PLoS One. 2013. PMID: 23826207 Free PMC article.
-
Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency.Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22. Mol Genet Metab. 2007. PMID: 16996289 Free PMC article. Review.
-
Deficits in neuronal cytochrome P450 activity attenuate opioid analgesia but not opioid side effects.Eur J Pharmacol. 2014 Oct 5;740:255-62. doi: 10.1016/j.ejphar.2014.07.028. Epub 2014 Jul 22. Eur J Pharmacol. 2014. PMID: 25062792 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources