Integrity and barrier function of the epidermis critically depend on glucosylceramide synthesis.

摘要: Ceramides are vital components of the water barrier in mammalian skin. Epidermis-specific, a major ceramide portion contains ω-hydroxy very long chain fatty acids (C30–C36). These ceramides (Cers) found extracellular lamellae stratum corneum either as linoleic acyl esters or protein bound. Glucosylceramide is glycosphingolipid epidermis. Synthesized from and UDP-glucose, it thought to be itself an intracellular precursor carrier for ceramides. To investigate whether GlcCer obligatory intermediate metabolism maintain epidermal function, mouse with epidermis-specific glucosylceramide synthase (Ugcg) deficiency has been generated. Four days after birth animals devoid synthesis keratinocytes showed pronounced desquamation extreme transepidermal loss leading death. The appeared thick unstructured mass. Lamellar bodies granulosum did not display usual ordered inner structure were often irregularly arranged. Although total amount protein-bound remained unchanged, epidermal-free increased 4-fold sphingomyelins, almost detectable wild type epidermis, emerged quantities comparable lost GlcCer. We conclude that transient formation regular arrangement lipids proteins lamellar maintenance barrier.