{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:28:44Z","timestamp":1786516124187,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Protein\u2010bound ceramides are a specialized subclass of ceramides that are essential for skin barrier function, and their defective formation leads to severe skin disorder ichthyosis. Despite their biological importance, the precise molecular structures of protein\u2010bound ceramides have remained incompletely defined, largely due to the technical challenges arising from their unique covalent linkage between lipid and protein components with highly distinct physicochemical properties. We investigated whether epoxy\u2010ketone (EpK)\u2013type protein\u2010bound ceramides present in mouse epidermis are conserved in human skin. Mass spectrometric analyses of epoxy\u2010enone (EpE) acylceramides reversibly released from EpK\u2010type protein\u2010bound ceramides revealed only low levels in human stratum corneum. Instead, much higher amounts of dihydroxy\u2010enone (DiHE) acylceramides were detected, indicating that dihydroxy\u2010ketone (DiHK)\u2013type protein\u2010bound ceramides are predominant in human skin. In contrast, DiHK\u2010type protein\u2010bound ceramides were present in mouse epidermis at much lower levels. DiHE acylceramides appeared as two chromatographically distinct peaks, which likely correspond to putative stereoisomers with (9\n                    <jats:italic>R<\/jats:italic>\n                    ,10\n                    <jats:italic>S<\/jats:italic>\n                    ) and (9\n                    <jats:italic>R<\/jats:italic>\n                    ,10\n                    <jats:italic>R<\/jats:italic>\n                    ) configurations. Age\u2010dependent increases in the (9\n                    <jats:italic>R<\/jats:italic>\n                    ,10\n                    <jats:italic>S<\/jats:italic>\n                    ) form in mouse epidermis closely paralleled changes in the expression levels of the epoxide hydrolase\n                    <jats:italic>Ephx3<\/jats:italic>\n                    , suggesting a role for EPHX3 in the conversion of epoxy\u2010type ceramides to dihydroxy\u2010type ceramides through epoxide ring opening. Together, these findings reveal molecular diversity in protein\u2010bound ceramides and a fundamental difference between human and mouse epidermal lipid architectural organization.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602245r","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:34:21Z","timestamp":1785958461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Dihydroxy\u2010Ketone\u2013Type Protein\u2010Bound Ceramides as the Dominant Type in Human Stratum Corneum"],"prefix":"10.1096","volume":"40","author":[{"given":"Ayumi","family":"Kojima","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Hokkaido University  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