A beta2-microglobulin cleavage variant fibrillates at near-physiological pH.
Biochem Biophys Res Commun
; 381(2): 187-91, 2009 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-19232323
ABSTRACT
Beta2-microglobulin (beta2m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of beta2m are still largely unknown. In vitro, acidic conditions, pH < 4.5, induce amyloid fibrillation of native beta2m within several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of beta2m--found in the circulation of many dialysis patients--is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects with intact, native beta2m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of beta2m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils of this variant is required to induce fibrillation of native beta2m. This may explain the apparent lack of detectable amounts of the variant beta2m in extracts of amyloid from DRA patients.
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Complementares:
Homeopatia
Assunto principal:
Artrite
/
Microglobulina beta-2
/
Amiloide
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Dinamarca