Kinetic analysis of the polymerization and depolymerization of beta(2)-microglobulin-related amyloid fibrils in vitro.
beta(2)-Microglobulin-related (Abeta(2)M) amyloidosis is a serious complication in patients on long-term dialysis, and partial unfolding of beta(2)-microglobulin (beta(2)-m) is believed to be prerequisite to its assembly into Abeta(2)M amyloid fibrils. Many kinds of amyloid-associated molecules (e.g., apolipoprotein E (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the development of Abeta(2)M amyloidosis. The formation of Abeta(2)M amyloid fibrils in vitro was first observed at low pH (2.0-3.0). Very recently, low concentrations of 2,2,2-trifluoroethanol (TFE) and the sub-micellar concentration of sodium dodecyl sulfate, a model for anionic phospholipids, have been reported to cause the extension of Abeta(2)M amyloid fibrils at a neutral pH, inducing partial unfolding of beta(2)-m and stabilization of the fibrils. Moreover, apoE, GAGs and PGs were found to stabilize Abeta(2)M amyloid fibrils at a neutral pH, forming a stable complex with the fibrils. Some GAGs, especially heparin enhanced the fibril extension in the presence of TFE at a neutral pH. Some PGs, especially biglycan also induced the polymerization of acid-denatured beta(2)-m. These findings are consistent with the hypothesis that in vivo, specific molecules that affect the conformation and stability of beta(2)-m and amyloid fibrils will have significant effects on the deposition of Abeta(2)M amyloid fibrils.
Yamamoto
Suguru
S
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8510, Japan.
Hasegawa
Kazuhiro
K
Yamaguchi
Itaru
I
Goto
Yuji
Y
Gejyo
Fumitake
F
Naiki
Hironobu
H
D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D020836:Protein Structure, Quaternary; D011509:Proteoglycans / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014270:Trifluoroethanol / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000737:chemistry*
D000682:Amyloid; D001057:Apolipoproteins E; D006025:Glycosaminoglycans; D011509:Proteoglycans; D001613:beta 2-Microglobulin; D012967:Sodium Dodecyl Sulfate; D014270:Trifluoroethanol