title: Role of epidermis-type lipoxygenases for skin barrier function and adipocyte differentiation.
abstract: 12R-lipoxygenase (12R-LOX) and epidermis-type LOX-3 (eLOX-3) are novel members of the multigene family of mammalian LOX. A considerable gap exists between the identification of these enzymes and their biologic function. Here, we present evidence that 12R-LOX and eLOX-3, acting in sequence, and eLOX-3 in combination with another, not yet identified LOX are critically involved in terminal differentiation of keratinocytes and adipocytes, respectively. Mutational inactivation of 12R-LOX and/or eLOX-3 has been found to be associated with development of an inherited ichthyosiform skin disorder in humans and genetic ablation of 12R-LOX causes a severe impairment of the epidermal lipid barrier in mice leading to post-natal death of the animals. In preadipocytes, a LOX-dependent PPARgamma activating ligand is released into the cell supernatant early upon induction of differentiation and available evidence indicates that this ligand is an eLOX-3-derived product. In accordance with this data is the observation that forced expression of eLOX-3 enhances adipocyte differentiation.
authors.affiliation: Research Group Eicosanoids and Tumor Development, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fürstenberger
authors.forename: Nikolas
authors.initials: N
authors.lastname: Epp
authors.forename: Katja-Martina
authors.initials: KM
authors.lastname: Eckl
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Claus
authors.initials: C
authors.lastname: Jørgensen
authors.forename: Philip
authors.initials: P
authors.lastname: Hallenborg
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Peter
authors.initials: P
authors.lastname: Krieg
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000201:enzymology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology*; D002454:Cell Differentiation; D004817:Epidermis / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D007057:Ichthyosis / Q000235:genetics / Q000503:physiopathology; D015603:Keratinocytes / Q000166:cytology; D008084:Lipoxygenase / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010539:Permeability; D012879:Skin Physiological Phenomena
chemical_list: C511051:ALOXE3 protein, human; D008084:Lipoxygenase; C518403:eLOX3 protein, mouse; D001092:Arachidonate 12-Lipoxygenase