Document Detail

Heparan sulfate mediates amyloid-beta internalization and cytotoxicity.
MedLine Citation:
PMID:  20053627     Owner:  NLM     Status:  MEDLINE    
Heparan sulfate (HS) has been found associated with amyloid deposits, including the toxic amyloid-beta (Abeta) peptide aggregates in cerebral vasculature and neuronal tissues in patients with Alzheimer's disease. However, the pathophysiological significance of the HS-Abeta interaction has remained unclear. In the present study, we applied cell models to gain insight into the roles of HS in relation to Abeta toxicity. Wild-type Chinese hamster ovary (CHO-WT) cells showed loss of viability following exposure to Abeta40, whereas the HS-deficient cell line, pgsD-677, was essentially resistant. Immunocytochemical analysis showed Abeta internalization by CHO-WT, but not pgsD-677 cells. Abeta40 toxicity was also attenuated in human embryonic kidney cells overexpressing heparanase. Finally, addition of heparin to human umbilical vein endothelial cells prevented internalization of added Abeta40 and protected against Abeta toxicity. Taken together, these findings suggest that cell-surface HS mediates Abeta internalization and toxicity.
Elina Sandwall; Paul O'Callaghan; Xiao Zhang; Ulf Lindahl; Lars Lannfelt; Jin-Ping Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-05
Journal Detail:
Title:  Glycobiology     Volume:  20     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-08     Completed Date:  2010-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  533-41     Citation Subset:  IM    
Department of Medical Biochemistry and Microbiology, University of Uppsala, The Biomedical Center, Box 582, SE-751 23, Uppsala, Sweden.
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MeSH Terms
Amyloid beta-Protein / metabolism*,  toxicity*
CHO Cells
Cell Survival / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Endothelial Cells / drug effects,  metabolism
Glucuronidase / biosynthesis,  metabolism
Heparin / pharmacology
Heparitin Sulfate / metabolism*
Structure-Activity Relationship
Reg. No./Substance:
0/Amyloid beta-Protein; 9005-49-6/Heparin; 9050-30-0/Heparitin Sulfate; EC 3.2.1.-/heparanase; EC

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