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ID 112323
著者
Kameyama, Hirokazu Tokushima University
Nakajima, Hiroyuki Tokushima University
Mikawa, Shiho Tokushima University|Kyoto Pharmaceutical University
Uchimura, Kenji Nagoya University
Kobayashi, Norihiro Kobe Pharmaceutical University
斎藤, 博幸 Kyoto Pharmaceutical University KAKEN研究者をさがす
資料タイプ
学術雑誌論文
抄録
The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1–83) of apoA-I containing this mutation deposit as amyloid fibrils in patients’ tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
6
開始ページ
30391
発行日
2016-07-28
備考
Supplementary Information : srep_6_30391_s1.pdf
権利情報
© The Author(s) 2016
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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言語
eng
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出版社版
部局
医学系
薬学系