ArticleThe Journal of clinical investigation2020
SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 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
- Biallelic GLTP mutations cause nonsyndromic epidermal differentiation disorder via disrupted epidermal glucosylceramide transport.The Journal of clinical investigation · 2026Article
- Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.The Journal of biological chemistry · 2026Article
- Skin Barrier Dysfunction in Contact and Atopic Dermatitis: A Comparative Review.Allergy, asthma & immunology research · 2026Review
- A standardized approach to test missenseJID innovations : skin science from molecules to population health · 2026Article
- Linoleic acid concentration at the air-liquid interface is key for optimal incorporation into skin model lipidome.Frontiers in physiology · 2026Article
- Palmoplantar Keratoderma: A Mechanism-Based Disease Classification.Clinical, cosmetic and investigational dermatology · 2026Article
- Analysis of the Thiol Adduction of Linoleate 9,10-Dihydroxy-11ACS omega · 2025Article
- Relationship between time-dependent epidermal ceramide composition changes and skin barrier function in adult mice.Molecular biology of the cell · 2025Article
- Linoleic acid improves rosacea through repairing mitochondrial damage in keratinocytes.Life medicine · 2025Article
- Niacinamide and its impact on stratum corneum hydration and structure.Scientific reports · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Skin Lipid Barrier: Structure, Function and Metabolism.Allergy, asthma & immunology research · 2024Review
- Correlations between Skin Condition Parameters and Ceramide Profiles in the Stratum Corneum of Healthy Individuals.International journal of molecular sciences · 2024Article
- Determining the structure of protein-bound ceramides, essential lipids for skin barrier function.iScience · 2023Article
- 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
- Cell biology of protein-lipid conjugation.Cell structure and function · 2023Review
- The Roles of sPLABiomolecules · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The corneocyte lipid envelope, composed of covalently bound ceramides and fatty acids, is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative liquid chromatography-mass spectometry (LC-MS) assays revealed almost complete loss of a species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy-11E-13-ketone, a reactive moiety known for its nonenzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.
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Registered trials
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 Socratic graph.