文章基本信息

标题：Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts
本地全文：下载
作者：Befekadu Asfaw ; Detlev Schindler ; Jana Ledvinová 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：1998
卷号：39
期号：9
页码：1768-1780
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The degradation of blood group glycolipid A-6-2 (GalNAc(α1 3)[Fucα1 2]Gal(β1 4)GlcNAc(β1 3)Gal (β1 4)Glc(β1 1′)Cer, IV²-α-fucosyl-IV³-α-N-acetylgalactosaminylneolactotetraosylceramide), tritium-labeled in its ceramide moiety, was studied in situ, in skin fibroblast cultures from normal controls, from patients with defects of lysosomal α-N-acetylgalactosaminidase, and from patients with other lysosomal storage diseases. Uptake of the glycolipid with apolipoprotein E-coated liposomes was linear with time and with the amount of glycolipid added. In normal cells, the expected array of less polar products and some lipids resulting from re-using the liberated sphingosine, mainly sphingomyelin and phosphatidylcholine, were formed. In α-N-acetylgalactosaminidase-deficient cells, the glycolipid was virtually not degraded; product formation was less than 2% of the normal control rate, suggesting that blood group A-active glycolipids contribute as storage compounds to the pathogenesis of this disease. The expected accumulation of degradation intermediates was seen in fucosidosis, and in Sandhoff, Gaucher, and Farber disease cells, whereas normal turnover rates were found in Tay-Sachs disease cells, G_M2 activator-deficient (variant AB of G_M2 gangliosidosis) and in sulfatide activator- ( sap -B-) deficient cells. In G_M1 gangliosidosis and in sap precursor-deficient cells, the lysosomal glycolipid catabolism was found to be strongly retarded; accumulation of individual products could not be seen. Skin fibroblasts from patients with α-N-acetylgalactosaminidase deficiency (Schindler disease) cannot degrade the major blood group A glycolipid.— Asfaw, B., D. Schindler, J. Ledvinová, B. Černý, F. Šmíd, and E. Conzelmann. Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts. J. Lipid. Res. 1998. 39: 1768–1780.
关键词：Schindler disease ; α-N-acetylgalactosaminidase deficiency ; fucosidase ; sphingolipid activator proteins ; fibroblasts ; in situ metabolism