Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
ReviewThe role of lipoxygenases in epidermis☆
Introduction
An important role of fatty acid (FA) metabolism in skin has been suggested since the discovery that essential fatty acids (EFA) and their products are involved in the normal process of forming the water-impermeable barrier in skin. Dietary deficiency of EFA results in characteristic scaly skin disorder and excessive water loss [1]. The addition of certain FA such as linoleic acid to the diet could reverse some of the cutaneous symptoms of EFA deficiency and several lines of evidence suggested that the curative effects of EFA in the EFA deficient animal involve the lipoxygenase (LOX)-catalyzed conversion of polyunsaturated fatty acids (PUFA) to oxygenated products [2], [3].
Shortly after the discovery of the first mammalian LOX [4] LOX activities and LOX products have been found in human and murine skin and epidermal cells as well [5]. Since then, a plethora of findings characterized the mammalian epidermis as a tissue with highly abundant and diverse LOX metabolism. LOX products identified in skin include a variety of oxidized free PUFA, arachidonic acid metabolites such as 12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyeicosatetraenoic acid (15-HETE), hepoxilins, trioxilins, and leukotrienes, and linoleic acid products such as 13-hydroxyoctadecadienoic acid (13-HODE) and 9-hydroxyoctadecadienoic acid (9-HODE) as well as docosahexaenoic acid-derived metabolites. LOX are also known to oxidize esterified structural lipids such as ceramides which in particular play an essential role in barrier function.
Section snippets
Mammalian lipoxygenases
LOX are a class of widely distributed non-heme iron containing dioxygenases that catalyze the stereo- and regio-specific incorporation of molecular oxygen into PUFA containing a (cis,cis)-1,4-pentadiene system. The primary products of LOX reactions are hydroperoxides which are rapidly transformed into their reduced hydroxyl analogs and products of subsequent enzymatic reactions (for reviews, see [6], [7]). The members of the LOX multigene family exhibit highly conserved gene and protein
Lipoxygenases in human and mouse skin: cloning, expression, activity and function
All LOX are expressed in skin of both humans and mice as detected by activity, immunohistochemistry and/or polymerase chain reaction (PCR) of the corresponding mRNA.
As key enzymes in the production of a variety of signaling lipid metabolites individual LOX isozymes are thought to play a role in the modulation of epithelial proliferation and/or differentiation as well as in inflammation, wound healing, inflammatory skin diseases and cancer. Emerging evidence furthermore indicates a structural
12R-LOX/eLOX-3 pathway in permeability barrier function
The discovery of two previously unknown LOX isoforms in skin that exhibit unconventional enzymatic features has paved the way to new insights into the role of LOX metabolism in epithelial tissue homeostasis demonstrating a pivotal role of a unique LOX pathway in the establishment and maintenance of the epidermal permeability barrier.
Acknowledgments
This work was supported by grants from the Deutsche Forschungsgemeinschaft (KR 905/6-2, KR 905/7-1).
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This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.