Linoleate-Containing Acylglucosylceramide, Acylceramide, and Events Associated with Formation of the Epidermal Permeability Barrier

Abstract

Background: Linoleate-containing acylglucosylceramide (GLC-CER[EOx], where x = sphingosine (S), dihydrosphingosine (dS), phytosphingosine (P) or 6-hydroxysphingosine (H)) in the viable epidermis serve as the precursors to the linoleate-containing acylceramides (CER[EOx]) in the stratum corneum (SC) and the cornified lipid envelope (CLE), both of which are essential for the barrier function of the skin. Summary: CLE formation and envelope maturation takes place across the SC. Hypoxic conditions in the epidermis and anaerobic glycolysis with production of lactic acid are important in proper SC barrier formation. Key Message: The CLE formation forms across the stratum corneum. Its formation from linoleate-containing acylglucosylceramide requires lipoxygenase action, but anaerobic conditions leading to lactate production and hypoxia-inducible factors are essential for proper barrier formation. A number of unanswered questions are raised regarding formation of the CLE and the epidermal permeability barrier.