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Human leukocyte glycosylasparaginase: cell‐to‐cell transfer and properties in correction of aspartylglycosaminuria
Author(s) -
Dunder Ulla,
Mon Ilkka
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02526-1
Subject(s) - cell , endocytosis , extracellular , enzyme , receptor , biology , microbiology and biotechnology , mannose , enzyme replacement therapy , chemistry , biochemistry , disease , medicine , pathology
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.