JCB logo
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online April 2, 2007
doi:10.1083/jcb.200612116
The Journal of Cell Biology, Vol. 177, No. 1, 173-182
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Epp et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Epp, N.
Right arrow Articles by Krieg, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Epp, N.
Right arrow Articles by Krieg, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 12R-lipoxygenase deficiency disrupts epidermal barrier function

Nikolas Epp1, Gerhard Fürstenberger1, Karsten Müller1, Silvia de Juanes1, Michael Leitges2, Ingrid Hausser3, Florian Thieme4, Gerhard Liebisch4, Gerd Schmitz4, and Peter Krieg1

1 Section Eicosanoids and Tumor Development, German Cancer Research Center, D-69120 Heidelberg, Germany
2 The Biotechnology Centre of Oslo, University of Oslo, N-0317, Oslo, Norway
3 Dermatological Department, University Clinic Heidelberg, D-69115 Heidelberg, Germany
4 Institute of Clinical Chemistry, University of Regensburg, D-93042 Regensburg, Germany

Correspondence to Peter Krieg: p.krieg{at}dkfz.de

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.

Abbreviations used in this paper: ARCI, autosomal recessive congenital ichthyosis; CE, cornified envelope; E, embryonic day; eLOX-3, epidermis-type LOX-3; ES, embryonic stem; HPETE, hydroperoxyeicosatetraenoic acid; LOX, lipoxygenase; PPAR, peroxisome proliferator-activated receptor; TEWL, transepidermal water loss.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents