Accumulation of protein-bound epidermal glucosylceramides in beta-glucocerebrosidase deficient type 2 Gaucher mice

The epidermal permeability barrier for water is essentially maintained by e xtracellular lipid membranes within the interstices of the stratum corneum. Ceramides, the main components of these membranes, derive in large part fr om hydrolysis of glucosylceramides mediated by the lysosomal enzyme beta-gl ucocerebrosidase. As analyzed in this work, the beta-glucocerebrosidase def iciency in type 2 Gaucher mice (RecNci I) resulted in an accumulation of al l epidermal glucosylceramide species accompanied with a decrease of the rel ated ceramides, However, the levels of one ceramide subtype, which possesse s an alpha-hydroxypalmitic acid, was not altered in RecNci I mice suggestin g that the beta-glucocerebrosidase pathway is not required for targeting of this lipid to interstices of the stratum corneum, Most importantly, omega- hydroxylated glucosylceramides which are protein-bound to the epidermal cor nified cell envelope of the transgenic mice accumulated up to 35-fold where as levels of related protein-bound ceramides and fatty acids were decreased to 100% of normal control. These data support the hypothesis that in wild- type epidermis omega-hydroxylated glucosylceramides are first transferred e nzymatically from their linoleic esters to proteins of the epidermal cornif ied cell envelope and then catabolized to protein-bound ceramides and fatty acids, thus contributing at least in part to the formation of the lipid-bo und envelope. (C) 1999 Federation of European Biochemical Societies.