{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:24:14Z","timestamp":1791267854713,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,6,9]]},"abstract":"<jats:p>\n                    A recognized feature of psoriasis and other proliferative dermatoses is accumulation in the skin of the unusual arachidonic acid metabolite, 12\n                    <jats:italic>R<\/jats:italic>\n                    -hydroxyeicosatetraenoic acid (12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE). This hydroxy fatty acid is opposite in chirality to the product of the well-known 12\n                    <jats:italic>S<\/jats:italic>\n                    -lipoxygenase and heretofore in mammals is known only as a product of cytochrome P450s. Here we provide mechanistic evidence for a lipoxygenase route to 12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE in human psoriatic tissue and describe a 12\n                    <jats:italic>R<\/jats:italic>\n                    -lipoxygenase that can account for the biosynthesis. Initially we demonstrated retention of the C-12 deuterium of octadeuterated arachidonic acid in its conversion to 12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE in incubations of psoriatic scales, indicating the end product is not formed by isomerization from 12\n                    <jats:italic>S<\/jats:italic>\n                    -H(P)ETE via the 12-keto derivative. Secondly, analysis of product formed from [10\n                    <jats:sub>R<\/jats:sub>\n                    -\n                    <jats:sup>3<\/jats:sup>\n                    H] and [10\n                    <jats:sub>S<\/jats:sub>\n                    -\n                    <jats:sup>3<\/jats:sup>\n                    H]-labeled arachidonic acids revealed that 12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE synthesis is associated with stereospecific removal of the pro-\n                    <jats:italic>R<\/jats:italic>\n                    hydrogen from the 10-carbon of arachidonate. This result is compatible with 12\n                    <jats:italic>R<\/jats:italic>\n                    -lipoxygenase-catalyzed formation of 12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE and not with a P450-catalyzed route to 12\n                    <jats:italic>R<\/jats:italic>\n                    -HETE in psoriatic scales. We cloned a lipoxygenase from human keratinocytes; the cDNA and deduced amino acid sequences share \u226450% identity to other human lipoxygenases. This enzyme, when expressed in Hela cells, oxygenates arachidonic acid to 12-HPETE, &gt;98% 12\n                    <jats:italic>R<\/jats:italic>\n                    in configuration. The 12\n                    <jats:italic>R<\/jats:italic>\n                    -lipoxygenase cDNA is detectable by PCR in psoriatic scales and as a 2.5-kilobase mRNA by Northern analysis of keratinocytes. Identification of this enzyme extends the known distribution of\n                    <jats:italic>R<\/jats:italic>\n                    -lipoxygenases to humans and presents an additional target for potential therapeutic interventions in psoriasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.12.6744","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"6744-6749","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":156,"title":["A 12\n                    <i>R<\/i>\n                    -lipoxygenase in human skin: Mechanistic evidence, molecular cloning, and expression"],"prefix":"10.1073","volume":"95","author":[{"given":"William E.","family":"Boeglin","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 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