| Theme | Dialysis -- related amyloidosis -- update | |
|---|---|---|
| Title | Effect of AGE-modified Beta2-m on A Beta2-m amyloid fibril extension in vitro | |
| Publish Date | 2001/01 | |
| Author | Norikazu Hashimoto | Department of Clinical and Laboraroty Medicine, Fukui Medical University |
| Author | Hironobu Naiki | Department of Pathology, Fukui Medical University |
| Author | Haruyoshi Yoshida | Department of Clinical and Laboraroty Medicine, Fukui Medical University |
| Author | Fumitake Gejyo | Department of Medicine (II), Niigata University School of Medicine |
| [ Summary ] | Beta2-microglobulin (beta2-m) is a major constituent of amyloid fibrils (fAbeta2-m) deposited in patients with A amyloidosis. Lately, several advanced glycation end products (AGE) structures of and fAbeta2-m have been suggested to play an important role in the pathogenesis of Abeta2-m amyloidosis. Actually, immunohistochemical studies of amyloid-deposited tissue have revealed a patchy distribution of the AGE-modified area in the amyloid deposits. Then we modified native beta2-m with D-glucose and investigated the effect of these modification on fAbeta2-m extension in vitro, using the recently established first-order kinetic model of fA extension in vitro. Western blot analysis with a monoclonal anti-AGE antibody showed that these glucose-modified beta2-m contained AGE (AGE-beta2-m). During the incubation of fAbeta2-m with native beta2-m atb37 centigrade, the fluorescence of thioflavin T increased withoutba lag phase and proceeded to equilibrium. By contrast, very poor increase in fluorescence was observed during the incubation of fAbeta2-m with AGE-beta2-m. Be sides, AGE-beta2-m exhibited a dose-dependent inhibitory effect on the extension reaction of fAbeta2-m with native beta2-m. These results may suggest that the modification of beta2-m with AGE would be a secondary event of fAbeta2-m deposition in vivo, thus would not play a promoting role in the formation of fAbeta2-m in vivo. | |