Chromium(III) ion and thyroxine cooperate to stabilize the transthyretin tetramer and suppress in vitro amyloid fibril formation.
Transthyretin (TTR) amyloid fibril formation, which is triggered by the dissociation of tetrameric TTR, appears to be the causative factor in familial amyloidotic polyneuropathy and senile systemic amyloidosis. Binding of thyroxine (T(4)), a native ligand of TTR, stabilizes the tetramer, but the bioavailability of T(4) for TTR binding is limited due to the preferential binding of T(4) to globulin, the major T(4) carrier in plasma. Here, we show that Cr(3+) increased the T(4)-binding capacity of wild-type (WT) and amyloidogenic V30M-TTR. Moreover, we demonstrate that Cr(3+) and T(4) cooperatively suppressed in vitro fibril formation due to the stabilization of WT-TTR and V30M-TTR.
Sato
Takashi
T
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Ando
Yukio
Y
Susuki
Seiko
S
Mikami
Fumi
F
Ikemizu
Shinji
S
Nakamura
Masaaki
M
Suhr
Ole
O
Anraku
Makoto
M
Kai
Toshiya
T
Suico
Mary Ann
MA
Shuto
Tsuyoshi
T
Mizuguchi
Mineyuki
M
Yamagata
Yuriko
Y
Kai
Hirofumi
H
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D002857:Chromium / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D017354:Point Mutation; D011228:Prealbumin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D013974:Thyroxine / Q000378:metabolism*
D000682:Amyloid; D011228:Prealbumin; D002857:Chromium; D013974:Thyroxine