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Suppression of amyl...
Suppression of amyloid beta a11-immunoreactivity by vitamin C: possible role of heparan sulfate oligosaccharides derived from glypican-1 by ascorbate-induced, no-catalyzed degradation.
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- Cheng, Fang (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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Cappai, Roberto (author)
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Ciccotosto, Giuseppe D (author)
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- Svensson Birkedal, Gabriel (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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Multhaup, Gerd (author)
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- Fransson, Lars-Åke (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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- Mani, Katrin (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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(creator_code:org_t)
- 2011
- 2011
- English.
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In: Journal of Biological Chemistry. - 1083-351X. ; 286:31, s. 27559-27572
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Abstract
Subject headings
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- Amyloid beta is generated from the copper- and heparan sulfate (HS)-binding amyloid precursor protein (APP) by proteolytic processing. APP supports S-nitrosylation of the HS-proteoglycan glypican-1 (Gpc-1). In the presence of ascorbate there is NO-catalyzed release of anhydromannose (anMan)-containing oligosaccharides from Gpc-1-SNO. We have investigated whether these oligosaccharides interact with amyolid beta during APP processing and plaque formation. anMan-Immunoreactivity was detected in amyloid plaques of Alzheimer (AD) and APP transgenic (Tg2576) mouse brains by immunofluorescence microscopy. APP/APP degradation products detected by antibodies to the C-terminus of APP, but not amyolid beta oligomers detected by the anti-amyloid beta A11 antibody, colocalized with anMan-immunoreactivity in Tg2576 fibroblasts. A 50-55-kDa anionic, SDS-stable, anMan- and amyloid beta-immunoreactive species was obtained from Tg2576 fibroblasts using immunoprecipitation with anti-APP (C-terminal). anMan-Containing HS oligo- and disaccharide preparations modulated or suppressed A11-immunoreactivity and oligomerization of amyloid beta 42 peptide in an in vitro assay. A11 immunoreactivity increased in Tg2576 fibroblasts when Gpc-1 autoprocessing was inhibited by U18666A, and decreased when Gpc-1 autoprocessing was stimulated by ascorbate. Neither overexpression of Gpc-1 in Tg2576 fibroblasts nor addition of copper ion and NO-donor to hippocampal slices from 3xTg-AD mice affected A11 immunoreactivity levels. However, A11 immunoreactivity was greatly suppressed by the subsequent addition of ascorbate. We speculate that temporary interaction between the amyolid beta domain and small, anMan-containing oligosaccharides may preclude formation of toxic amyloid beta oligomers. A portion of the oligosaccharides co-secrete with the amyloid beta peptides and are deposited in plaques. These results support the notion that inadequate supply of vitamin C could contribute to late onset AD in humans.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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