The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier

Muñoz-Garcia, Agustí, Thomas, Christopher P. ORCID: https://orcid.org/0000-0001-5840-8613, Keeney, Diane S., Zheng, Yuxiang and Brash, Alan R. 2014. The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1841 (3) , pp. 401-408. 10.1016/j.bbalip.2013.08.020

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Abstract

This review covers the background to discovery of the two key lipoxygenases (LOX) involved in epidermal barrier function, 12R-LOX and eLOX3, and our current views on their functioning. In the outer epidermis, their consecutive actions oxidize linoleic acid esterified in ω-hydroxy-ceramide to a hepoxilin-related derivative. The relevant background to hepoxilin and trioxilin biochemistry is briefly reviewed. We outline the evidence that linoleate in the ceramide is the natural substrate of the two LOX enzymes and our proposal for its importance in construction of the epidermal water barrier. Our hypothesis is that the oxidation promotes hydrolysis of the oxidized linoleate moiety from the ceramide. The resulting free ω-hydroxyl of the ω-hydroxyceramide is covalently bound to proteins on the surface of the corneocytes to form the corneocyte lipid envelope, a key barrier component. Understanding the role of the LOX enzymes and their hepoxilin products should provide rational approaches to ameliorative therapy for a number of the congenital ichthyoses involving compromised barrier function. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Publisher:	Elsevier
ISSN:	1388-1981
Date of First Compliant Deposit:	5 December 2016
Date of Acceptance:	30 August 2013
Last Modified:	09 Nov 2023 09:36
URI:	https://orca.cardiff.ac.uk/id/eprint/90841

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