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ID 113750
Title Alternative
Iron-induced atrophy via Akt-FOXO3-E3 Ubiquitin ligase pathway
Author
Imao, Mizuki Tokushima University
Satoh, Akiho Tokushima University
Watanabe, Hiroaki Tokushima University
Hamano, Hirofumi Tokushima University
Keywords
Iron
Skeletal muscle atrophy
Atrogenes
Content Type
Journal Article
Description
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.
Journal Title
Journal of Trace Elements in Medicine and Biology
ISSN
0946672X
18783252
NCID
AA11067337
AA12084444
Publisher
Elsevier
Volume
35
Start Page
66
End Page
76
Published Date
2016-01-28
Rights
© 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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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
Author
departments
Medical Sciences
Pharmaceutical Sciences