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PubMed · 16198304

Hepoxilin A3 synthase.

Santosh Nigam·Maria-Patapia Zafiriou
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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.

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8,11,14-Eicosatrienoic AcidAmino Acid SequenceAnimalsArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseCell Line, TumorIntramolecular OxidoreductasesLipoxygenase InhibitorsMolecular Sequence DataNeoplasm ProteinsRatsSequence AlignmentJournal ArticleResearch Support, Non-U.S. Gov'tReview

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Santosh Nigam, Maria-Patapia Zafiriou. 2005-09-21. Hepoxilin A3 synthase.. https://doi.org/10.1016/j.bbrc.2005.09.065

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