July 21, 2011

Give me some skin

A new understanding of the biochemical pathway that builds our skin barrier could lead to treatments for skin diseases.

skin cross section

Our skin stands between us and our environment – it protects us from pathogens and forms a barrier to water loss. Defects in the water barrier can result in dry, thickened, scaly skin – symptoms of a group of mostly genetic skin diseases called ichthyoses.

The essential fatty acid linoleate and two epidermal lipoxygenase enzymes (12R-LOX and eLOX3) are required for formation of the mammalian skin barrier – deficiencies in linoleate or either enzyme cause skin disease. However, the precise roles of these key players are poorly understood.

Now, in a Journal of Biological Chemistry “Paper of the Week,” Alan Brash and colleagues report a novel biochemical pathway by which 12R-LOX and eLOX3 act on linoleate to generate the skin barrier. The researchers demonstrate that the enzymes oxidize linoleate linked to ceramide. This releases the linoleate and frees the ceramide to bind to protein and form the “corneocyte lipid envelope,” a crucial component of the epidermal barrier. Understanding this pathway has implications for the treatment of ichthyoses.

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the National Institute of Child Health and Human Development.