Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen

Annalisa Relini, Silvia De Stefano, Silvia Torrassa, Ornella Cavalleri, Ranieri Rolandi, Alessandra Gliozzi, Sofia Giorgetti, Sara Raimondi, Loredana Marchese, Laura Verga, Antonio Rossi, Monica Stoppini, Vittorio Bellotti

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Abstract

The tissue specificity of fibrillar deposition in dialysis-related amyloidosis is most likely associated with the peculiar interaction of β2-microglobulin (β2-m) with collagen fibers. However, other co-factors such as glycosaminoglycans might facilitate amyloid formation. In this study we have investigated the role of heparin in the process of collagen-driven amyloidogenesis. In fact, heparin is a well known positive effector of fibrillogenesis, and the elucidation of its potential effect in this type of amyloidosis is particularly relevant because heparin is regularly given to patients subject to hemodialysis to prevent blood clotting. We have monitored by atomic force microscopy the formation of β2-m amyloid fibrils in the presence of collagen fibers, and we have discovered that heparin strongly accelerates amyloid deposition. The mechanism of this effect is still largely unexplained. Using dynamic light scattering, we have found that heparin promotes β2-m aggregation in solution at pH 6.4. Morphology and structure of fibrils obtained in the presence of collagen and heparin are highly similar to those of natural fibrils. The fibril surface topology, investigated by limited proteolysis, suggests that the general assembly of amyloid fibrils grown under these conditions and in vitro at low pH is similar. The exposure of these fibrils to trypsin generates a cleavage at the C-terminal of lysine 6 and creates the 7-99 truncated form of β2-m (ΔN6β2-m) that is a ubiquitous constituent of the natural β2-m fibrils. The formation of this β2-m species, which has a strong propensity to aggregate, might play an important role in the acceleration of local amyloid deposition.

Original languageEnglish
Pages (from-to)4912-4920
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
Publication statusPublished - Feb 22 2008

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Collagen Type I
Amyloid
Heparin
Collagen
Amyloidosis
Proteolysis
Organ Specificity
Dialysis
Fibers
Atomic Force Microscopy
Blood Coagulation
Dynamic light scattering
Glycosaminoglycans
Trypsin
Lysine
Renal Dialysis
Atomic force microscopy
Blood
Agglomeration
Topology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Relini, A., De Stefano, S., Torrassa, S., Cavalleri, O., Rolandi, R., Gliozzi, A., ... Bellotti, V. (2008). Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. Journal of Biological Chemistry, 283(8), 4912-4920. https://doi.org/10.1074/jbc.M702712200

Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. / Relini, Annalisa; De Stefano, Silvia; Torrassa, Silvia; Cavalleri, Ornella; Rolandi, Ranieri; Gliozzi, Alessandra; Giorgetti, Sofia; Raimondi, Sara; Marchese, Loredana; Verga, Laura; Rossi, Antonio; Stoppini, Monica; Bellotti, Vittorio.

In: Journal of Biological Chemistry, Vol. 283, No. 8, 22.02.2008, p. 4912-4920.

Research output: Contribution to journalArticle

Relini, A, De Stefano, S, Torrassa, S, Cavalleri, O, Rolandi, R, Gliozzi, A, Giorgetti, S, Raimondi, S, Marchese, L, Verga, L, Rossi, A, Stoppini, M & Bellotti, V 2008, 'Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen', Journal of Biological Chemistry, vol. 283, no. 8, pp. 4912-4920. https://doi.org/10.1074/jbc.M702712200
Relini, Annalisa ; De Stefano, Silvia ; Torrassa, Silvia ; Cavalleri, Ornella ; Rolandi, Ranieri ; Gliozzi, Alessandra ; Giorgetti, Sofia ; Raimondi, Sara ; Marchese, Loredana ; Verga, Laura ; Rossi, Antonio ; Stoppini, Monica ; Bellotti, Vittorio. / Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 8. pp. 4912-4920.
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AU - Rolandi, Ranieri

AU - Gliozzi, Alessandra

AU - Giorgetti, Sofia

AU - Raimondi, Sara

AU - Marchese, Loredana

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AU - Rossi, Antonio

AU - Stoppini, Monica

AU - Bellotti, Vittorio

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