TY - JOUR
T1 - Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II
AU - Chiba, Takuya
AU - Kogishi, Kumiko
AU - Wang, Jing
AU - Xia, Cher
AU - Matsushita, Takatoshi
AU - Miyazaki, Jun Ichi
AU - Saito, Izumu
AU - Hosokawa, Masanori
AU - Higuchi, Keiichi
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1999/10
Y1 - 1999/10
N2 - Apolipoprotein A-II (apoA-II), the second most abundant apolipoprotein of serum high density lipoprotein, deposits as an amyloid fibril (AApoAII) in old mice. Mouse strains with a high incidence of senile amyloidosis have the type C apoA-II gene (Apoa2(c)), whereas the strains with a low incidence of amyloidosis have the type B apoA-II gene (Apoa2b). In this study, to investigate whether the type B apoA-II protein inhibits the extension of amyloid fibrils, we constructed an adenovirus vector bearing the Apoa2b cDNA (Adex1CATApoa2b), which is expressed under the control of a hepatocyte- specific promoter. The mice were infected with Adex1CATApoa2b before induction of amyloidosis by the injection of AApoAII amyloid fibril seeds. Compared with the mice infected with the control virus, amyloid deposition was suppressed significantly in the mice infected with Adex1CATApoa2b. Fluorometry using thioflavine T also revealed that AApoAII fibril extension was inhibited by the addition of type B apoA-II in vitro. Thus, we propose that Apoa2b contributes as an active inhibitor of amyloid fibril extension and overexpression of amyloid-resistant gene variant may be an attractive therapeutic target in amyloidosis.
AB - Apolipoprotein A-II (apoA-II), the second most abundant apolipoprotein of serum high density lipoprotein, deposits as an amyloid fibril (AApoAII) in old mice. Mouse strains with a high incidence of senile amyloidosis have the type C apoA-II gene (Apoa2(c)), whereas the strains with a low incidence of amyloidosis have the type B apoA-II gene (Apoa2b). In this study, to investigate whether the type B apoA-II protein inhibits the extension of amyloid fibrils, we constructed an adenovirus vector bearing the Apoa2b cDNA (Adex1CATApoa2b), which is expressed under the control of a hepatocyte- specific promoter. The mice were infected with Adex1CATApoa2b before induction of amyloidosis by the injection of AApoAII amyloid fibril seeds. Compared with the mice infected with the control virus, amyloid deposition was suppressed significantly in the mice infected with Adex1CATApoa2b. Fluorometry using thioflavine T also revealed that AApoAII fibril extension was inhibited by the addition of type B apoA-II in vitro. Thus, we propose that Apoa2b contributes as an active inhibitor of amyloid fibril extension and overexpression of amyloid-resistant gene variant may be an attractive therapeutic target in amyloidosis.
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U2 - 10.1016/S0002-9440(10)65234-0
DO - 10.1016/S0002-9440(10)65234-0
M3 - Article
C2 - 10514414
AN - SCOPUS:0032878280
VL - 155
SP - 1319
EP - 1326
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -