Establishment of immortalized Schwann cells from Fabry mice and their low uptake of recombinant α-galactosidase
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- 作者：Ikuo Kawashima ; Kazuhiko Watabe ; Youichi Tajima ; Tomoko Fukushige ; Tamotsu Kanzaki ; Takuro Kanekura ; Kanako Sugawara ; Naho Ohyanagi ; Toshihiro Suzuki and Tadayasu Togawa ; et al.
- 关键词：Fabry disease ; Schwann cell ; α ; Galactosidase ; Globotriaosylceramide ; Enzyme replacement therapy ; Cation ; independent mannose 6 ; phosphate receptor
- 刊名：Journal of Human Genetics
- 出版年：2007
- 出版时间：December, 2007
- 年：2007
- 卷：52
- 期：12
- 页码：1018-1025
- 全文大小：448.8 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Human Genetics
Molecular Medicine
Cancer Research
Cell Biology
Immunology
Neurosciences - 出版者：Springer Japan
- ISSN：1435-232X
文摘
Peripheral neuropathy is one of the important manifestations of Fabry disease. Enzyme replacement therapy with presently available recombinant α-galactosidases does not always improve the Fabry neuropathy. But the reason has not been determined yet. We established a Schwann cell line from Fabry mice, characterized it, and then examined the uptake of α-galactosidase by cells and its effect on the degradation of accumulated substrate. The cells exhibited a distinct Schwann cell morphology and biochemical phenotype (α-Galactosidase activity was deficient, and numerous cytoplasmic inclusion bodies were present in the cells). A recombinant α-galactosidase added to the culture medium was incorporated into the cultured Fabry Schwann cells dose dependently. But the increase in cell-associated enzyme activity was less than that in the cases of human and mouse Fabry fibroblasts. The administration of a high dose of the enzyme improved the pathological changes in cells, although a low dose of it did not. Cellular uptake of the enzyme was strongly inhibited in the presence of mannose 6-phosphate. This suggests that the enzyme is incorporated via cation-independent mannose 6-phosphate receptors in Schwann cells. The low expression of cation-independent mannose 6-phosphate receptors in Schwann cells must be one of the reasons their uptake of the present enzymes was low. The administration of a high dose of the enzyme or the development of an enzyme containing many mannose 6-phosphate residues is required to improve Fabry neuropathy.