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The heparan sulfate...
The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease
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Smits, Nicole C. (author)
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- Kurup, Sindhulakshmi (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Rops, Angelique L. (author)
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Ten Dam, Gerdy B. (author)
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Massuger, Leon F. (author)
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Hafmans, Theo (author)
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Turnbull, Jeremy E. (author)
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- Spillmann, Dorothe (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Li, Jin-Ping (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Kennel, Stephen J. (author)
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Wall, Jonathan S. (author)
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Shworak, Nicholas W. (author)
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Dekhuijzen, P. N. Richard (author)
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van der Vlag, Johan (author)
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van Kuppevelt, Toin H. (author)
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(creator_code:org_t)
- 2010
- 2010
- English.
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:52, s. 41143-41151
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Heparan sulfate (HS) is a structurally complex polysaccharide that interacts with a broad spectrum of extracellular effector ligands and thereby is thought to regulate a diverse array of biologic processes. The specificity of HS-ligand interactions is determined by the arrangement of sulfate groups on HS, which creates distinct binding motifs. Biologically important HS motifs are expected to exhibit regulated expression. Yet, there is a profound lack of tools to identify such motifs; consequently, little is known of their structures and functions. We have identified a novel phage display-derived antibody (NS4F5) that recognizes a highly regulated HS motif (HS(NS4F5)), which we have rigorously identified as (GlcNS6S-IdoA2S)(3). HS(NS4F5) exhibits a restricted expression in healthy adult tissues. Blocking HS(NS4F5) on cells in culture resulted in reduced proliferation and enhanced sensitivity to apoptosis. HS(NS4F5) is upregulated in tumor endothelial cells, consistent with a role in endothelial cell activation. Indeed, TNF-α stimulated endothelial expression of HS(NS4F5), which contributed to leukocyte adhesion. In a mouse model of severe systemic AA amyloidosis, HS(NS4F5) was expressed within amyloid deposits, which were successfully detected by microSPECT imaging using NS4F5 as a molecularly targeted probe. Combined, our results demonstrate that NS4F5 is a powerful tool for elucidating the biological function of HS(NS4F5) and can be exploited as a probe to detect novel polysaccharide biomarkers of disease processes.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Biochemistry
- Biokemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Smits, Nicole C.
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Kurup, Sindhulak ...
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Rops, Angelique ...
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Ten Dam, Gerdy B ...
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Massuger, Leon F ...
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Hafmans, Theo
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show more...
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Turnbull, Jeremy ...
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Spillmann, Dorot ...
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Li, Jin-Ping
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Kennel, Stephen ...
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Wall, Jonathan S ...
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Shworak, Nichola ...
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Dekhuijzen, P. N ...
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van der Vlag, Jo ...
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van Kuppevelt, T ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Journal of Biolo ...
- By the university
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Uppsala University