Role of VLDL/chylomicron in amyloid formation in familial amyloidotic polyneuropathy.
We examined the affinity of transthyretin (TTR) for lipoproteins and the effect of lipoproteins on TTR-related amyloidogenesis using serum samples from healthy volunteers and patients with familial amyloidotic polyneuropathy (FAP) ATTRVal30Met. In both volunteers and patients, TTR levels were highest in the VLDL fraction containing chylomicrons (VLDL/CM) and next highest in the HDL fraction. Levels were lowest in the LDL fraction. Mass spectrometric analyses of TTR spectra revealed significant TTR association with VLDL/CM and the levels of variant TTR were decreased in the FAP patients. Examination of the affinity of wild-type and variant TTRs for lipoprotein via a quartz crystal microbalance (QCM) revealed the highest affinity of both proteins for VLDL/CM. In in vitro amyloid formation test measured with thioflavin T and electron microscopy, in the presence of VLDL/CM, amyloid formation of TTR was enhanced more than in the presence LDL or in the absence of lipoprotein species. These results suggest that TTR should be highly associated especially with VLDL/CM and amyloidogenicity of TTR should be enhanced around the adipocytes.
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Xuguo
X
Sun
Yukio
Y
Ando
Katsuki
K
Haraoka
Shoichi
S
Katsuragi
Taro
T
Yamashita
Sonoka
S
Yamashita
Miyo
M
Okajima
Hisayasu
H
Terazaki
Hiroaki
H
Okabe
D000328:Adult; D000682:Amyloid / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000378:metabolism*; D002914:Chylomicrons / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012016:Reference Values
D000682:Amyloid; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D011228:Prealbumin