Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II

Takuya Chiba, Kumiko Kogishi, Jing Wang, Cher Xia, Takatoshi Matsushita, Jun Ichi Miyazaki, Izumu Saito, Masanori Hosokawa, Keiichi Higuchi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1319-1326
Number of pages8
JournalAmerican Journal of Pathology
Volume155
Issue number4
Publication statusPublished - 1999 Oct
Externally publishedYes

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Apolipoprotein A-II
Amyloid
Adenoviridae
Amyloidosis
Genes
Fluorometry
Apolipoproteins
Incidence
HDL Lipoproteins
Hepatocytes
Seeds
Complementary DNA
Viruses
Injections
Serum

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Chiba, T., Kogishi, K., Wang, J., Xia, C., Matsushita, T., Miyazaki, J. I., ... Higuchi, K. (1999). Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II. American Journal of Pathology, 155(4), 1319-1326.

Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II. / Chiba, Takuya; Kogishi, Kumiko; Wang, Jing; Xia, Cher; Matsushita, Takatoshi; Miyazaki, Jun Ichi; Saito, Izumu; Hosokawa, Masanori; Higuchi, Keiichi.

In: American Journal of Pathology, Vol. 155, No. 4, 10.1999, p. 1319-1326.

Research output: Contribution to journalArticle

Chiba, T, Kogishi, K, Wang, J, Xia, C, Matsushita, T, Miyazaki, JI, Saito, I, Hosokawa, M & Higuchi, K 1999, 'Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II', American Journal of Pathology, vol. 155, no. 4, pp. 1319-1326.
Chiba, Takuya ; Kogishi, Kumiko ; Wang, Jing ; Xia, Cher ; Matsushita, Takatoshi ; Miyazaki, Jun Ichi ; Saito, Izumu ; Hosokawa, Masanori ; Higuchi, Keiichi. / Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II. In: American Journal of Pathology. 1999 ; Vol. 155, No. 4. pp. 1319-1326.
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