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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylglucosamine / analogs & derivatives
-
Acetylglucosamine / metabolism*
-
Aspartylglucosaminuria
-
Aspartylglucosylaminase / genetics
-
Aspartylglucosylaminase / metabolism*
-
Cell Line, Transformed
-
Coculture Techniques
-
Culture Media, Conditioned / metabolism
-
Endocytosis* / drug effects
-
Fibroblasts / cytology
-
Fibroblasts / drug effects
-
Fibroblasts / metabolism
-
Fluorescent Antibody Technique
-
Herpesvirus 4, Human / physiology
-
Humans
-
Leukocytes / cytology
-
Leukocytes / drug effects
-
Leukocytes / enzymology*
-
Leukocytes / metabolism
-
Lymphocytes / cytology
-
Lymphocytes / drug effects
-
Lymphocytes / enzymology
-
Lymphocytes / metabolism
-
Lysosomal Storage Diseases / enzymology*
-
Lysosomal Storage Diseases / genetics
-
Lysosomes / drug effects
-
Lysosomes / metabolism
-
Mannosephosphates / metabolism
-
Mannosephosphates / pharmacology
-
Protein Transport / drug effects
-
Receptor, IGF Type 2 / metabolism
-
Y Chromosome / genetics
Substances
-
Culture Media, Conditioned
-
Mannosephosphates
-
Receptor, IGF Type 2
-
N-acetylglucosaminylasparagine
-
mannose-6-phosphate
-
Aspartylglucosylaminase
-
Acetylglucosamine