Quantitation of the rabbit intestinal glycolipid receptor for Shiga toxin. Further evidence for the developmental regulation of globotriaosylceramide in microvillus membranes.
Quantitation of the rabbit intestinal glycolipid receptor for Shiga toxin. Further evidence for the developmental regulation of globotriaosylceramide in microvillus membranes.
复制标题
志贺毒素兔肠道糖脂受体的定量。
DOI：
10.1016/0016-5085(89)90074-7
复制
发表时间：
1989
期刊：
影响因子：
29.4
通讯作者：
Keusch,GT
中科院分区：
文献类型：
--
作者：
Mobassaleh,M;Gross,SK;McCluer,RH;Donohue-Rolfe,A;Keusch,GT
由志贺菌1型产生的滋贺毒素可引起肠毒性、细胞毒性和神经毒性作用，其可能由糖脂受体神经酰胺三己糖基酯（Gb 3）介导。为了研究该受体与毒素作用的关系，对不同年龄兔小肠微绒毛膜中的神经酰胺三己糖苷进行了定量和进一步表征。从兔微绒毛膜中提取糖脂，在Unisil柱上纯化，并通过高效液相色谱法定量。主要糖脂峰为含羟基化脂肪酸的葡萄糖神经酰胺、乳糖神经酰胺和globotriaosylceramide。随着年龄的增长，globotriaosylceramide水平显著增加，新生儿和成人分别为0.02 - 16.2 pmol/μg微绒毛膜蛋白。α-半乳糖苷酶处理可使乳糖神经酰胺峰升高，但34日龄家兔中的神经酰胺三己糖苷峰含量显著降低。碘化滋贺毒素与globotriaosylceramide的结合通过放射自显影在高效薄层色谱板上记录。因此，兔微绒毛膜中滋贺毒素的糖脂受体是一种含羟基化脂肪酸的神经酰胺三己糖。这部分在新生儿中几乎不存在，并随着年龄的增长而逐渐增加。三己糖神经酰胺的数量差异可能是兔肠组织对滋贺毒素的功能反应性随年龄而异的潜在基础。
Shiga toxin, produced byShigella dysenteriae 1, causes enterotoxic, cytotoxic, and neurotoxic effects, which may be mediated by a glycolipid receptor, globotriaosylceramide, Gb3. To study the relationship of this receptor and toxin effects, globotriaosylceramide was quantitated and further characterized in rabbit small intestinal microvillus membranes at various ages. Glycolipids were extracted from rabbit microvillus membranes, purified on Unisil columns, and quantitated by highperformance liquid chromatography. The major glycolipid peaks were hydroxylated fatty acid-containing glucosylceramide, lactosylceramide, and globotriaosylceramide. There was a marked increase of globotriaosylceramide levels with age, ranging from 0.02 to 16.2 pmol/μg microvillus membrane protein in neonates and adults, respectively. The globotriaosylceramide peak was susceptible to α-galactosidase treatment, which produced an elevation in the lactosylceramide peak, but markedly reduced globotriaosylceramide content in 34-day-old rabbits. Binding of iodinated Shiga toxin to globotriaosylceramide was documented on highperformance thin-layer chromatography plates by autoradiography. The glycolipid receptor for Shiga toxin in rabbit microvillus membranes is thus a hydroxylated fatty acid-containing globotriaosylceramide. This moiety is virtually absent in neonates and gradually increases with age. Quantitative differences in globotriaosylceramide may be the underlying basis for the age-specific differences in functional responsiveness of rabbit intestinal tissue to Shiga toxin.
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