Rawlings, Anthony V;
Lane, Majella E;
Voegeli, Rainer;
(2024)
The importance of stratum corneum ω-inoleoyloxyacylceramides in human skin barrier health: their biochemistry, processing enzymes and metabolites involved in corneocyte lipid envelope maturation.
International Journal of Cosmetic Science
, 46
(4)
pp. 623-642.
10.1111/ics.12955.
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Lane_the importance of stratum corneum_AAM.pdf - Accepted Version Access restricted to UCL open access staff until 8 August 2025. Download (2MB) |
Abstract
Over the past 50 years there have been great strides made in the discovery of the composition and relevance of the total stratum corneum (SC) ceramide matrix. However, the focus of this review is on the free intercellular class of ω-linoleoyloxyacylceramides, corneocyte-bound ceramides and associated lipids known as the corneocyte lipid envelope (CLE) together with their processing enzymes involved in aiding ceramide attachment the corneocyte protein envelope (CPE). Two structural models and partially shared biosynthetic pathways have been proposed for the attachment of CPE-bound O-ceramides (ω-hydroxyceramides attached to glutamate residues of proteins in the (CPE) using the 12R-lipoxygenase (12R-LOX)/epidermal lipoxygenase-3 (eLOX3)/epoxide hydrolase-3 (EPHX3)/unknown esterase/ transglutaminase-1 (TG1) attachment pathway) and CPE-bound EO-ceramides (epoxy-enone ceramides attached to cysteine residues of proteins in the CPE using the 12R-LOX/eLOX3/short chain dehydrogenase/reductase family 9C member 7 (SDR9C7)/non-enzymatic attachment pathway), i.e. there is a bifurcation step beyond epidermal eLOX3. Their formation and structures will be discussed as well as their relevance in compromised skin barrier conditions together with our own work on SC maturation examined by proteomics, lipidomics, enzyme immunolocalization studies, mechanical fragility assays and Nile red staining of corneocyte envelopes (CE). Reduced levels of 12R-LOX, eLOX3, SDR9C7 and TG1 were observed in photodamaged skin of the cheeks that were associated with reduced SC maturation as evidenced by Nile red staining and increased CE fragility. In the severely photodamaged cheeks of Albino African SC we also observed increased levels of acylceramides. Concomitantly by reducing the activity of 12R-LOX by antibody inhibition and TG1 inhibition with a known chemical inhibitor, we demonstrated in a humidity-based ex vivo SC maturation model that these enzymes contributed to increased CE hydrophobicity and mechanical integrity. We hypothesize that at least the CPE-bound O-ceramide pathway is operational in the SC. Nevertheless, our understanding of the full complexity of ω-linoleoyloxyacylceramides and the composition of the CLE is limited particularly on cosmetically relevant body sites such as the face.
Type: | Article |
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Title: | The importance of stratum corneum ω-inoleoyloxyacylceramides in human skin barrier health: their biochemistry, processing enzymes and metabolites involved in corneocyte lipid envelope maturation |
Location: | England |
DOI: | 10.1111/ics.12955 |
Publisher version: | https://doi.org/10.1111/ics.12955 |
Language: | English |
Additional information: | This version is the author-accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Humans, Ceramides, Skin, Epidermis |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
URI: | https://discovery.ucl.ac.uk/id/eprint/10195766 |
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