ArticleThe Journal of biological chemistry2011
Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases-Review Article.Frontiers in medicine · 2021Pooled it
- Discovery of Dihydroxy-Ketone-Type Protein-Bound Ceramides as the Dominant Type in Human Stratum Corneum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Reactivity of mammalian lipoxygenases (ALOX isoforms) with phospholipids, biomembranes and lipoproteins.Communications biology · 2026Article
- Activation and execution of lipoxygenase catalysis.Redox biochemistry and chemistry · 2026Article
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- ALOXE3 missense variant in a Chihuahua with autosomal recessive ichthyosis.Animal genetics · 2025Article
- Analysis of the Thiol Adduction of Linoleate 9,10-Dihydroxy-11ACS omega · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- The stratum corneum barrier: impaired function in relation to associated lipids and proteins.Tissue barriers · 2025Review
- The Role of Linoleic Acid in Skin and Hair Health: A Review.International journal of molecular sciences · 2024Review
- Identification ofInternational journal of molecular sciences · 2024Article
- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Determining the structure of protein-bound ceramides, essential lipids for skin barrier function.iScience · 2023Article
- Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.International journal of molecular sciences · 2023Review
- Evaluation of ω-alkynyl-labeled linoleic and arachidonic acids as substrates for recombinant lipoxygenase pathway enzymes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.JID innovations : skin science from molecules to population health · 2023Article
- Article
- Changes in levels of omega-O-acylceramides and related processing enzymes of sun-exposed and sun-protected facial stratum corneum in differently pigmented ethnic groups.International journal of cosmetic science · 2022Article
- Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions.Progress in lipid research · 2022Review
- Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology.Frontiers in pharmacology · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
A barrier to water loss is vital to maintaining life on dry land. Formation of the mammalian skin barrier requires both the essential fatty acid linoleate and the two lipoxygenases 12R-lipoxygenase (12R-LOX) and epidermal lipoxygenase-3 (eLOX3), although their roles are poorly understood. Linoleate occurs in O-linoleoyl-ω-hydroxyceramide, which, after hydrolysis of the linoleate moiety, is covalently attached to protein via the free ω-hydroxyl of the ceramide, forming the corneocyte lipid envelope, a scaffold between lipid and protein that helps seal the barrier. Here we show using HPLC-UV, LC-MS, GC-MS, and (1)H NMR that O-linoleoyl-ω-hydroxyceramide is oxygenated in a regio- and stereospecific fashion by the consecutive actions of 12R-LOX and eLOX3 and that these products occur naturally in pig and mouse epidermis. 12R-LOX forms 9R-hydroperoxy-linoleoyl-ω-hydroxyceramide, further converted by eLOX3 to specific epoxyalcohol (9R,10R-trans-epoxy-11E-13R-hydroxy) and 9-keto-10E,12Z esters of the ceramide; an epoxy-ketone derivative (9R,10R-trans-epoxy-11E-13-keto) is the most prominent oxidized ceramide in mouse skin. These products are absent in 12R-LOX-deficient mice, which crucially display a near total absence of protein-bound ω-hydroxyceramides and of the corneocyte lipid envelope and die shortly after birth from transepidermal water loss. We conclude that oxygenation of O-linoleoyl-ω-hydroxyceramide is required to facilitate the ester hydrolysis and allow bonding of the ω-hydroxyceramide to protein, providing a coherent explanation for the roles of multiple components in epidermal barrier function. Our study uncovers a hitherto unknown biochemical pathway in which the enzymic oxygenation of ceramides is involved in building a crucial structure of the epidermal barrier.
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Registered trials
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