Isolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils.
AffiliationDepartment of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
MetadataShow full item record
AbstractAmyloid fibrils were isolated by extraction in water from the livers and spleens of four patients who had died of monoclonal, light-chain (AL)-type, systemic amyloidosis and one with reactive systemic, amyloid A protein (AA)-type amyloidosis. Each fibril preparation contained 1-2% by weight of glycosaminoglycan (GAG) which was tightly associated with the fibrils and not just co-isolated from the tissues with them. After exhaustive digestion of the fibrils with papain and Pronase, the GAGs were specifically precipitated with cetylpyridinium chloride and were identified by cellulose acetate electrophoresis and selective susceptibility to specific glycosidases. All the preparations contained approximately equal amounts of heparan sulphate and dermatan sulphate. There was no evidence for the presence of chondroitin sulphate or other GAGs. Fine structural analysis by oligosaccharide mapping in gradient polyacrylamide gels, following partial digestion with specific glycosidases, showed very similar structures among the heparan sulphates and the dermatan sulphates, respectively. GAGs were also extracted by solubilizing amyloid fibrils in 4 M-guanidinium chloride followed by CsCl density-gradient ultracentrifugation. Although a minor proportion of the GAG material obtained in this way was apparently in the form of proteoglycan molecules, most of it was free GAG chains. The presence in amyloid fibrils of different types, in different organs and from different patients of particular GAG classes with similar structures supports the view that these molecules may be of pathogenic significance.
CitationIsolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils. 1991, 275 ( Pt 1):67-73 Biochem. J.
- Macromolecular properties of glycosaminoglycans in primary AL amyloid fibril extracts of lymphoid tissue origin.
- Authors: Stenstad T, Magnus JH, Kolset SO, Cornwell GG 3rd, Husby G
- Issue date: 1991 Nov
- Identification of glycosaminoglycans in human renal and splenic secondary AA amyloid fibril preparations.
- Authors: Stenstad T, Magnus JH, Kolset SO, Husby G
- Issue date: 1991
- Glycosaminoglycans in extracts of cardiac amyloid fibrils from familial amyloid cardiomyopathy of Danish origin related to variant transthyretin Met 111.
- Authors: Magnus JH, Stenstad T, Kolset SO, Husby G
- Issue date: 1991 Jul
- Characterization of proteoglycans and glycosaminoglycans in bovine renal AA-type amyloidosis.
- Authors: Niewold TA, Flores Landeira JM, van den Heuvel LP, Ultee A, Tooten PC, Veerkamp JH
- Issue date: 1991
- A high resolution ultrastructural study of experimental murine AA amyloid.
- Authors: Inoue S, Kisilevsky R
- Issue date: 1996 Mar