Role of epidermis-type lipoxygenases for skin barrier function and adipocyte differentiation.
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.
Fürstenberger
Gerhard
G
Research Group Eicosanoids and Tumor Development, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Epp
Nikolas
N
Eckl
Katja-Martina
KM
Hennies
Hans Christian
HC
Jørgensen
Claus
C
Hallenborg
Philip
P
Kristiansen
Karsten
K
Krieg
Peter
P
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
C511051:ALOXE3 protein, human; D008084:Lipoxygenase; C518403:eLOX3 protein, mouse; D001092:Arachidonate 12-Lipoxygenase