Skip Navigation



Glycobiology Advance Access published online on September 1, 2004
Glycobiology, doi:10.1093/glycob/cwh145
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
15/1/79    most recent
cwh145v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kelo, E.
Right arrow Articles by Mononen, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelo, E.
Right arrow Articles by Mononen, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received June 21, 2004
Revised August 27, 2004
Accepted August 30, 2004

ORIGINAL ARTICLES

Massive accumulation of Man2GlcNac2-Asn in non-neuronal tissues of glycosylasparaginase-deficient mice and its removal by enzyme replacement therapy

Eira Kelo 1, Ulla Dunder 1, Ilkka Mononen 2*

1 Laboratory Centre, Kuopio University Hospital, FIN-70210 Kuopio, Finland
2 Department of Clinical Chemistry, University of Turku and TUCH Laboratories, PO Box 52, FIN-20521 Turku, Finland

* To whom correspondence should be addressed. E-mail: ilkka.mononen{at}tyks.fi.


  Abstract

Aspartylglycosaminuria (AGU) is caused by deficient enzymatic activity of glycosylasparaginase (GA). The disease is characterized by accumulation of aspartylglucosamine (GlcNAc-Asn) and other glycoasparagines in tissues and body fluids of AGU patients and in an AGU mouse model. In the current study, we characterized a glycoasparagine carrying the tetrasaccharide moiety of {alpha}-D-Man-(1->6)-{beta}-D-Man-(1->4)-{beta}-D-GlcNAc-(1->4)-{beta}-D-GlcNAc-(1->N)-Asn (Man2GlcNAc2-Asn) in urine of an AGU patient and also in the tissues of the AGU mouse model. Quantitative analysis demonstrated a massive accumulation of the compound especially in non-neuronal tissues of the AGU mice, in which the levels of Man2GlcNAc2-Asn were typically between 30-87 per cent of those of GlcNAc-Asn. The highest level of Man2GlcNAc2-Asn was found in the liver, spleen and heart tissues of the AGU mice, the respective amounts being 87, 76 and 57 per cent of the GlcNAc-Asn levels. In the brain tissue of AGU mice the Man2GlcNAc2-Asn storage was only 9% of that of GlcNAc-Asn. In contrast to GlcNAc-Asn, the storage of Man2GlcNAc2-Asn markedly increased in the liver and spleen tissues of AGU mice when they grew older. Enzyme replacement therapy with glycosylasparaginase for 3.5 weeks reduced the amount of Man2GlcNAc2-Asn by 66-97 per cent in non-neuronal tissues, but only by 13 per cent in the brain tissue of the AGU mice. In conclusion, there is evidence for a role for storage of glycoasparagines other than aspartylglucosamine in the pathogenesis of AGU and this possibility should be taken into consideration in the treatment of the disease.

Keywords: aspartylglucosaminuria; enzyme replacement; lysosomal enzymes; lysosomal storage; N-linked oligosaccharide.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.