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- Title
Heparan sulfate mediates amyloid-beta internalization and cytotoxicity.
- Authors
Sandwall, Elina; O'Callaghan, Paul; Xiao Zhang; Lindahl, Ulf; Lannfelt, Lars; Jin-Ping Li
- Abstract
Heparan sulfate (HS) has been found associated with amyloid deposits, including the toxic amyloid-beta (Aβ) peptide aggregates in cerebral vasculature and neuronal tissues in patients with Alzheimer's disease. However, the pathophysiological significance of the HS-Aβ interaction has remained unclear. In the present study, we applied cell models to gain insight into the roles of HS in relation to Aβ toxicity. Wild-type Chinese hamster ovary (CHO-WT) cells showed loss of viability following exposure to Aβ40, whereas the HS-deficient cell line, pgsD-677, was essentially resistant. Immunocytochemical analysis showed Aβ internalization by CHO-WT, but not pgsD-677 cells. Aβ40 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 Aβ40 and protected against Aβ toxicity. Taken together, these findings suggest that cell-surface HS mediates Aβ internalization and toxicity.
- Subjects
AMYLOID; ALZHEIMER'S patients; IMMUNOCYTOCHEMISTRY; SULFATES; AMYLOID beta-protein
- Publication
Glycobiology, 2010, Vol 20, Issue 5, p533
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cwp205