A {beta}{sub 2}-microglobulin cleavage variant fibrillates at near-physiological pH
- Department of Virology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen (Denmark)
- Department of International Health, Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark)
{beta}{sub 2}-microglobulin ({beta}{sub 2}m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of {beta}{sub 2}m are still largely unknown. In vitro, acidic conditions, pH < 4.5, induce amyloid fibrillation of native {beta}{sub 2}m within several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of {beta}{sub 2}m-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 {beta}{sub 2}m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of {beta}{sub 2}m 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 {beta}{sub 2}m. This may explain the apparent lack of detectable amounts of the variant {beta}{sub 2}m in extracts of amyloid from DRA patients.
- OSTI ID:
- 21255954
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 381, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2009.02.041; PII: S0006-291X(09)00270-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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