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Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

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タイトル: Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver
著者: Yamada, Yuma 著作を一覧する
Nakamura, Kohei 著作を一覧する
Abe, Jiro 著作を一覧する
Hyodo, Mamoru 著作を一覧する
Haga, Sanae 著作を一覧する
Ozaki, Michitaka 著作を一覧する
Harashima, Hideyoshi 著作を一覧する
キーワード: Mitochondria
Mitochondrial delivery
Antioxidant chemicals
Coenzyme Q(10)
Ischemia/reperfusion injury
MITO-Porter
In vivo delivery
発行日: 2015年 9月10日
出版者: Elsevier
誌名: Journal of controlled release
巻: 213
開始ページ: 86
終了ページ: 95
出版社 DOI: 10.1016/j.jconrel.2015.06.037
抄録: We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q(10) (CoQ(10)), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ(10) in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ(10)-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ(10)-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ(10)-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ(10) -MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ(10)-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ(10) via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies. (C) 2015 Elsevier B.V. All rights reserved.
Rights: © 2015, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/62775
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 山田 勇磨

 

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