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12R-lipoxygenase deficiency disrupts epidermal barrier function

12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital...

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Autores principales: Epp, Nikolas, Fürstenberger, Gerhard, Müller, Karsten, de Juanes, Silvia, Leitges, Michael, Hausser, Ingrid, Thieme, Florian, Liebisch, Gerhard, Schmitz, Gerd, Krieg, Peter
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064121/
https://www.ncbi.nlm.nih.gov/pubmed/17403930
http://dx.doi.org/10.1083/jcb.200612116
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author Epp, Nikolas
Fürstenberger, Gerhard
Müller, Karsten
de Juanes, Silvia
Leitges, Michael
Hausser, Ingrid
Thieme, Florian
Liebisch, Gerhard
Schmitz, Gerd
Krieg, Peter
author_facet Epp, Nikolas
Fürstenberger, Gerhard
Müller, Karsten
de Juanes, Silvia
Leitges, Michael
Hausser, Ingrid
Thieme, Florian
Liebisch, Gerhard
Schmitz, Gerd
Krieg, Peter
author_sort Epp, Nikolas
collection PubMed
description 12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX–deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired. This study indicates that the 12R-LOX–eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing.
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spelling pubmed-20641212007-11-29 12R-lipoxygenase deficiency disrupts epidermal barrier function Epp, Nikolas Fürstenberger, Gerhard Müller, Karsten de Juanes, Silvia Leitges, Michael Hausser, Ingrid Thieme, Florian Liebisch, Gerhard Schmitz, Gerd Krieg, Peter J Cell Biol Research Articles 12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX–deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired. This study indicates that the 12R-LOX–eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing. The Rockefeller University Press 2007-04-09 /pmc/articles/PMC2064121/ /pubmed/17403930 http://dx.doi.org/10.1083/jcb.200612116 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Epp, Nikolas
Fürstenberger, Gerhard
Müller, Karsten
de Juanes, Silvia
Leitges, Michael
Hausser, Ingrid
Thieme, Florian
Liebisch, Gerhard
Schmitz, Gerd
Krieg, Peter
12R-lipoxygenase deficiency disrupts epidermal barrier function
title 12R-lipoxygenase deficiency disrupts epidermal barrier function
title_full 12R-lipoxygenase deficiency disrupts epidermal barrier function
title_fullStr 12R-lipoxygenase deficiency disrupts epidermal barrier function
title_full_unstemmed 12R-lipoxygenase deficiency disrupts epidermal barrier function
title_short 12R-lipoxygenase deficiency disrupts epidermal barrier function
title_sort 12r-lipoxygenase deficiency disrupts epidermal barrier function
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064121/
https://www.ncbi.nlm.nih.gov/pubmed/17403930
http://dx.doi.org/10.1083/jcb.200612116
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