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标题：Uptake of a Recombinant Human α-L-Iduronidase (laronidase) by Cultured Fibroblasts and Osteoblasts
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作者：Takahiro Tsukimura ; Youichi Tajima ; Ikuo Kawashima 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：9
页码：1691-1695
DOI：10.1248/bpb.31.1691
出版社：The Pharmaceutical Society of Japan
摘要：To examine the uptake of a recombinant human α- L -iduronidase (laronidase) by cultured fibroblasts from a patient with mucopolysaccharidosis I (MPS I) and its effect on the cleavage of accumulated substrates, we performed enzymological, Western blotting, immunocytochemical and morphological studies. Laronidase was incorporated into the MPS I cells dose-dependently mainly via mannose 6-phosphate (M6P) receptors. Then the incorporated enzyme was transported to lysosomes and processed to the mature form, the pathological changes of the cells being improved. Furthermore, we compared the uptake of laronidase by cultured mouse osteoblasts with that by cultured mouse fibroblasts. The enzyme was incorporated into the cultured mouse osteoblasts mainly via M6P receptors, although mannose (Man) receptors were partially involved in the uptake of the enzyme, as in the cultured fibroblasts. But the uptake by the former was apparently lower than that by the latter. The administration of a high dose of the enzyme or development of a recombinant α- L -iduronidase containing many M6P residues is required for further improvement of enzyme replacement therapy for skeletal disorders caused by MPS I.
关键词：mucopolysaccharidosis I;α- L -iduronidase;osteoblast;enzyme replacement therapy;mannose 6-phosphate receptor