Accumulation of protein‐bound epidermal glucosylceramides in β‐glucocerebrosidase deficient type 2 Gaucher mice

FEBS Letters

Sandhoff, Konrad²  Doering, Thomas²  Proia, Richard L¹ 

[1] Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany

关键词: Glucocerebrosidase;    Gaucher disease;    Sphingolipid;    Epidermal permeability barrier;    Knockout mouse;   

DOI  :  10.1016/S0014-5793(99)00274-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The epidermal permeability barrier for water is essentially maintained by extracellular lipid membranes within the interstices of the stratum corneum. Ceramides, the main components of these membranes, derive in large part from hydrolysis of glucosylceramides mediated by the lysosomal enzyme β-glucocerebrosidase. As analyzed in this work, the β-glucocerebrosidase deficiency in type 2 Gaucher mice (RecNci I) resulted in an accumulation of all epidermal glucosylceramide species accompanied with a decrease of the related ceramides. However, the levels of one ceramide subtype, which possesses an α-hydroxypalmitic acid, was not altered in RecNci I mice suggesting that the β-glucocerebrosidase pathway is not required for targeting of this lipid to interstices of the stratum corneum. Most importantly, ω-hydroxylated glucosylceramides which are protein-bound to the epidermal cornified cell envelope of the transgenic mice accumulated up to 35-fold whereas levels of related protein-bound ceramides and fatty acids were decreased to 10% of normal control. These data support the hypothesis that in wild-type epidermis ω-hydroxylated glucosylceramides are first transferred enzymatically from their linoleic esters to proteins of the epidermal cornified cell envelope and then catabolized to protein-bound ceramides and fatty acids, thus contributing at least in part to the formation of the lipid-bound envelope.

【 授权许可】

Unknown