ID | 113750 |
タイトル別表記 | Iron-induced atrophy via Akt-FOXO3-E3 Ubiquitin ligase pathway
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著者 |
Imao, Mizuki
Tokushima University
Satoh, Akiho
Tokushima University
Watanabe, Hiroaki
Tokushima University
堀ノ内, 裕也
Tokushima University
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キーワード | Iron
Skeletal muscle atrophy
Atrogenes
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資料タイプ |
学術雑誌論文
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抄録 | Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal muscle atrophy is induced by an excess of iron, which is an essential trace metal for all living organisms. Excessive amounts of iron catalyze the formation of highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated group and the iron-injected group (10 mg iron·day-1·mouse-1) during 2 weeks. Mice in the iron-injected group showed an increase in the iron content of the skeletal muscle and serum and ferritin levels in the muscle, along with reduced skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3 pathway. Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress.
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掲載誌名 |
Journal of Trace Elements in Medicine and Biology
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ISSN | 0946672X
18783252
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cat書誌ID | AA11067337
AA12084444
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出版者 | Elsevier
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巻 | 35
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開始ページ | 66
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終了ページ | 76
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発行日 | 2016-01-28
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権利情報 | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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言語 |
eng
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著者版フラグ |
著者版
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部局 |
医学系
薬学系
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