Glycosaminoglycan and proteoglycan inhibit the depolymerization of β2-microglobulin amyloid fibrils in vitro
| Autor: | Naoki Tsuzuike, Naoki Takahashi, Yukiya Yamaguchi, Hironobu Naiki, Hironori Suda, Itaru Yamaguchi, Kazuhiro Hasegawa, Masaharu Seki, Suguru Yamamoto, Fumitake Gejyo, Kouichi Seto |
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| Rok vydání: | 2003 |
| Předmět: |
Amyloid
Polymers Decorin macromolecular substances Dermatan sulfate chemistry.chemical_compound medicine Humans Aggrecan Glycosaminoglycans amyloidosis murine proteoglycan Dose-Response Relationship Drug biology Heparin Amyloidosis Biglycan Heparan sulfate Hydrogen-Ion Concentration medicine.disease Recombinant Proteins carbohydrates (lipids) Microscopy Electron Spectrometry Fluorescence Proteoglycan chemistry Biochemistry Nephrology biology.protein Proteoglycans Thioflavin beta 2-Microglobulin |
| Zdroj: | Kidney International. 64:1080-1088 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.2003.00167.x |
| Popis: | Glycosaminoglycan and proteoglycan inhibit the depolymerization of β 2 -microglobulin amyloid fibrils in vitro. Background Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of β 2 -microglobulin–related (Aβ 2 m) amyloidosis, the precise roles of these molecules for the development of Aβ 2 m amyloidosis are poorly understood. Methods We investigated the effects of GAGs and PGs on the depolymerization of Aβ 2 m amyloid fibrils at a neutral pH, as well as on the formation of the fibrils at an acidic pH in vitro, using fluorescence spectroscopy with thioflavin T and electron microscopy. Results Depolymerization of Aβ 2 m amyloid fibrils at pH 7.5 at 37°C was inhibited dose-dependently by the presence of some GAGs (heparin, dermatan sulfate, or heparan sulfate) or PGs (biglycan, decorin, or keratan sulfate proteoglycan). Electron microscopy revealed that a significant amount of Aβ 2 m amyloid fibrils remained in the reaction mixture with some lateral aggregation. Second, when monomeric β 2 m was incubated with aggrecan, biglycan, decorin, or heparin at pH 2.5 at 37°C for up to 21days, the thioflavin T fluorescence increased depending on dose and time. Electron microscopy revealed the formation of rigid and straight fibrils similar to Aβ 2 m amyloid fibrils in β 2 m incubated with biglycan for 21days. Conclusion These results suggest that some GAGs and PGs could enhance the deposition of Aβ 2 m amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of β 2 m in the fibrils, as well as by acting as a scaffold for the polymerization of β 2 m into the fibrils. |
| Databáze: | OpenAIRE |
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