| Item type |
文献 / Documents(1) |
| 公開日 |
2020-07-17 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1002/jcsm.12202 |
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関連名称 |
10.1002/jcsm.12202 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Potential therapeutic interventions for chronic kidney disease‐associated sarcopenia via indoxyl sulfate‐induced mitochondrial dysfunction |
| タイトル別表記 |
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その他のタイトル |
Therapy for CKD-associated muscle dysfunction |
| 著者 |
エノキ, ユウキ
ワタナベ, ヒロシ
アラケ, リホ
フジムラ, ルイ
イシオドリ, カナ
イマフク, タダシ
ニシダ, ケント
スギモト, リュウセイ
ナガオ, サオリ
ミヤムラ, シゲユキ
異島, 優
タナカ, モトコ
マツシタ, カズタカ
コマバ, ヒロタカ
フカガワ, マサフミ
オタギリ, マサキ
マルヤマ, トオル
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| 抄録 |
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内容記述 |
Background
Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice.
Methods
The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups.
Results
In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level.
Conclusions
Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance. |
| キーワード |
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主題 |
Chronic kidney disease |
| キーワード |
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|
主題 |
Indoxyl sulfate |
| キーワード |
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|
主題 |
Muscle atrophy |
| キーワード |
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|
主題 |
Mitochondrial function |
| キーワード |
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|
主題 |
L-carnitine |
| キーワード |
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|
主題 |
Dipeptidyl peptidase-4 inhibitor |
| 書誌情報 |
en : Journal of Cachexia, Sarcopenia and Muscle
巻 8,
号 5,
p. 735-747,
発行日 2017-06-12
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
21906009 |
| 出版者 |
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出版者 |
John Wiley & Sons |
| 出版者 |
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|
出版者 |
The Society on Sarcopenia, Cachexia and Wasting Disorders |
| 権利情報 |
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|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| EID |
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|
識別子 |
334855 |
| 言語 |
|
|
言語 |
eng |
jcsm_8_5_735.pdf (710 KB)
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