title: Human leukocyte glycosylasparaginase: cell-to-cell transfer and properties in correction of aspartylglycosaminuria.
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.
authors: Department of Clinical Chemistry, Kuopio University Hospital, Finland. ulla.dunder@kuh.fi
authors: U
authors: U
authors: Dunder
authors: I
authors: I
authors: Mononen
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism*; D054880:Aspartylglucosaminuria; D001227:Aspartylglucosylaminase / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016464:Lysosomal Storage Diseases / Q000201:enzymology* / Q000235:genetics; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D014998:Y Chromosome / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C000009:N-acetylglucosaminylasparagine; C027693:mannose-6-phosphate; D001227:Aspartylglucosylaminase; D000117:Acetylglucosamine