ArticleProceedings of the National Academy of Sciences of the United States of America1998
A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 175 citations in OpenAlex.
- Activation and execution of lipoxygenase catalysis.Redox biochemistry and chemistry · 2026Article
- Allosteric properties of mammalian ALOX15 orthologs.The Journal of biological chemistry · 2026Review
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- Roles of Lipoxygenases in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- Review
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2024Review
- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Review
- The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae.Frontiers in cell and developmental biology · 2022Article
- Stable analogs of 13‑hydroxy-9,10-trans-epoxy-(11E)-octadecenoate (13,9-HEL), an oxidized derivative of linoleic acid implicated in the epidermal skin barrier.Prostaglandins, leukotrienes, and essential fatty acids · 2021Article
- Molecular Pathways Linking Oxylipins to Nociception in Rats.The journal of pain · 2021Article
- The enzymology of human eicosanoid pathways: the lipoxygenase branches.Molecular biology reports · 2020Review
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
- 12R-lipoxygenase activity is reduced in photodamaged facial stratum corneum. A novel activity assay indicates a key function in corneocyte maturation.International journal of cosmetic science · 2019Article
- Probing the Electrostatic and Steric Requirements for Substrate Binding in Human Platelet-Type 12-Lipoxygenase.Biochemistry · 2019Article
- Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.Progress in lipid research · 2019Review
- Characterization of Epidermal Lipoxygenase Expression in Normal Human Skin and Tissue-Engineered Skin Substitutes.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Endocervical and Neutrophil Lipoxygenases Coordinate Neutrophil Transepithelial Migration to Neisseria gonorrhoeae.The Journal of infectious diseases · 2018Article
- Hepatocyte ALOXE3 is induced during adaptive fasting and enhances insulin sensitivity by activating hepatic PPARγ.JCI insight · 2018Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
A recognized feature of psoriasis and other proliferative dermatoses is accumulation in the skin of the unusual arachidonic acid metabolite, 12R-hydroxyeicosatetraenoic acid (12R-HETE). This hydroxy fatty acid is opposite in chirality to the product of the well-known 12S-lipoxygenase and heretofore in mammals is known only as a product of cytochrome P450s. Here we provide mechanistic evidence for a lipoxygenase route to 12R-HETE in human psoriatic tissue and describe a 12R-lipoxygenase that can account for the biosynthesis. Initially we demonstrated retention of the C-12 deuterium of octadeuterated arachidonic acid in its conversion to 12R-HETE in incubations of psoriatic scales, indicating the end product is not formed by isomerization from 12S-H(P)ETE via the 12-keto derivative. Secondly, analysis of product formed from [10R-3H] and [10S-3H]-labeled arachidonic acids revealed that 12R-HETE synthesis is associated with stereospecific removal of the pro-R hydrogen from the 10-carbon of arachidonate. This result is compatible with 12R-lipoxygenase-catalyzed formation of 12R-HETE and not with a P450-catalyzed route to 12R-HETE in psoriatic scales. We cloned a lipoxygenase from human keratinocytes; the cDNA and deduced amino acid sequences share </=50% identity to other human lipoxygenases. This enzyme, when expressed in Hela cells, oxygenates arachidonic acid to 12-HPETE, >98% 12R in configuration. The 12R-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 R-lipoxygenases to humans and presents an additional target for potential therapeutic interventions in psoriasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.