Journal
PROSTAGLANDINS & OTHER LIPID MEDIATORS
Volume 82, Issue 1-4, Pages 128-134Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2006.05.006
Keywords
lipoxygenase; keratinocytes; terminal differentiation; ichthyosis; epidermal barrier; adipogenesis; peroxisome proliferator activated receptor
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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 PPAR gamma 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. (c) 2006 Elsevier Inc. All rights reserved.
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