Abstract |
Aspartylglycosaminuria (AGU), a severe lysosomal storage disease, is caused by the deficiency of the lysosomal enzyme, glycosylasparaginase (GA), and accumulation of aspartylglucosamine (GlcNAc-Asn) in tissues. Here we show that human leukocyte glycosylasparaginase can correct the metabolic defect in Epstein-Barr virus (EBV)-transformed AGU lymphocytes rapidly and effectively by mannose-6-phosphate receptor-mediated endocytosis or by contact-mediated cell-to-cell transfer from normal EBV-transformed lymphocytes, and that 2-7% of normal activity is sufficient to correct the GlcNAc-Asn metabolism in the cells. Cell-to-cell contact is obligatory for the transfer of GA since normal transformed lymphocytes do not excrete GA into extracellular medium. The combined evidence indicates that cell-to-cell transfer of GA plays a main role in enzyme replacement therapy of AGU by normal lymphocytes.
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Authors | U Dunder, I Mononen |
Journal | FEBS letters
(FEBS Lett)
Vol. 499
Issue 1-2
Pg. 77-81
(Jun 15 2001)
ISSN: 0014-5793 [Print] England |
PMID | 11418116
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Culture Media, Conditioned
- Mannosephosphates
- Receptor, IGF Type 2
- N-acetylglucosaminylasparagine
- mannose-6-phosphate
- Aspartylglucosylaminase
- Acetylglucosamine
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Topics |
- Acetylglucosamine
(analogs & derivatives, metabolism)
- Aspartylglucosaminuria
- Aspartylglucosylaminase
(genetics, metabolism)
- Cell Line, Transformed
- Coculture Techniques
- Culture Media, Conditioned
(metabolism)
- Endocytosis
(drug effects)
- Fibroblasts
(cytology, drug effects, metabolism)
- Fluorescent Antibody Technique
- Herpesvirus 4, Human
(physiology)
- Humans
- Leukocytes
(cytology, drug effects, enzymology, metabolism)
- Lymphocytes
(cytology, drug effects, enzymology, metabolism)
- Lysosomal Storage Diseases
(enzymology, genetics)
- Lysosomes
(drug effects, metabolism)
- Mannosephosphates
(metabolism, pharmacology)
- Protein Transport
(drug effects)
- Receptor, IGF Type 2
(metabolism)
- Y Chromosome
(genetics)
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