Apolipoprotein E inhibits the depolymerization of beta 2-microglobulin-related amyloid fibrils at a neutral pH.
beta 2-Microglobulin-related (A beta 2M) amyloidosis is a common and serious complication in patients on long-term hemodialysis, and beta 2-microglobulin (beta 2-m) is a major structural component of A beta 2M amyloid fibrils. Fluorescence spectroscopic analysis with thioflavin T and electron microscopic study revealed that A beta 2M amyloid fibrils readily depolymerize into monomeric beta 2-m at a neutral to basic pH. Circular dichroism analysis revealed that soon after the initiation of the depolymerization reaction at pH 7.5, the characteristic spectrum of beta 2-m in A beta 2M amyloid fibrils changes to resemble that of monomeric beta 2-m at pH 7.5. Apolipoprotein E (apoE), a representative amyloid-associated protein, formed a stable complex with A beta 2M amyloid fibrils and inhibited the depolymerization of A beta 2M amyloid fibrils dose-dependently in a range of 0--10 microM. These results showed that apoE could enhance the deposition of amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta 2-m in the fibrils.
Yamaguchi
I
I
Department of Pathology, Fukui Medical University, Fukui 910-1193, Japan.
Hasegawa
K
K
Takahashi
N
N
Gejyo
F
F
Naiki
H
H
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry* / Q000502:physiology; D002474:Cell-Free System; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011108:Polymers / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D011108:Polymers; D001613:beta 2-Microglobulin