Doering T, Proia R L, Sandhoff K
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Germany.
FEBS Lett. 1999 Mar 26;447(2-3):167-70. doi: 10.1016/s0014-5793(99)00274-4.
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 beta-glucocerebrosidase. As analyzed in this work, the beta-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 alpha-hydroxypalmitic acid, was not altered in RecNci I mice suggesting 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 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 omega-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.
水的表皮渗透屏障主要由角质层间隙中的细胞外脂质膜维持。神经酰胺是这些膜的主要成分，很大程度上源自溶酶体酶β-葡萄糖脑苷脂酶介导的葡萄糖神经酰胺水解。如本研究分析所示，2型戈谢病小鼠（RecNci I）中的β-葡萄糖脑苷脂酶缺乏导致所有表皮葡萄糖神经酰胺种类积累，同时相关神经酰胺减少。然而，一种含有α-羟基棕榈酸的神经酰胺亚型水平在RecNci I小鼠中未改变，这表明β-葡萄糖脑苷脂酶途径对于该脂质靶向角质层间隙并非必需。最重要的是，与转基因小鼠表皮角质化包膜蛋白结合的ω-羟基化葡萄糖神经酰胺积累高达35倍，而相关的蛋白结合神经酰胺和脂肪酸水平降至正常对照的10%。这些数据支持以下假设：在野生型表皮中，ω-羟基化葡萄糖神经酰胺首先通过酶促作用从其亚油酸酯转移至表皮角质化包膜蛋白，然后分解为蛋白结合神经酰胺和脂肪酸，从而至少部分有助于脂质结合包膜的形成。
