論文 - 詳細
| RRC ID | 51823 |
|---|---|
| 著者 | Enoki Y, Watanabe H, Arake R, Sugimoto R, Imafuku T, Tominaga Y, Ishima Y, Kotani S, Nakajima M, Tanaka M, Matsushita K, Fukagawa M, Otagiri M, Maruyama T. |
| タイトル | Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. |
| ジャーナル | Sci Rep |
| Abstract |
Skeletal muscle atrophy, referred to as sarcopenia, is often observed in chronic kidney disease (CKD) patients, especially in patients who are undergoing hemodialysis. The purpose of this study was to determine whether uremic toxins are involved in CKD-related skeletal muscle atrophy. Among six protein-bound uremic toxins, indole containing compounds, indoxyl sulfate (IS) significantly inhibited proliferation and myotube formation in C2C12 myoblast cells. IS increased the factors related to skeletal muscle breakdown, such as reactive oxygen species (ROS) and inflammatory cytokines (TNF-α, IL-6 and TGF-β1) in C2C12 cells. IS also enhanced the production of muscle atrophy-related genes, myostatin and atrogin-1. These effects induced by IS were suppressed in the presence of an antioxidant or inhibitors of the organic anion transporter and aryl hydrocarbon receptor. The administered IS was distributed to skeletal muscle and induced superoxide production in half-nephrectomized (1/2 Nx) mice. The chronic administration of IS significantly reduced the body weights accompanied by skeletal muscle weight loss. Similar to the in vitro data, IS induced the expression of myostatin and atrogin-1 in addition to increasing the production of inflammatory cytokines by enhancing oxidative stress in skeletal muscle. These data suggest that IS has the potential to accelerate skeletal muscle atrophy by inducing oxidative stress-mediated myostatin and atrogin-1 expression. |
| 巻・号 | 6 |
| ページ | 32084 |
| 公開日 | 2016-8-23 |
| DOI | 10.1038/srep32084 |
| PII | srep32084 |
| PMID | 27549031 |
| PMC | PMC4994088 |
| MeSH | Animals Antioxidants / pharmacology Cell Division / drug effects Cell Line Cytokines / biosynthesis Cytokines / genetics Disease Models, Animal Gene Expression Regulation / drug effects* Indican / toxicity* Male Mice Mice, Inbred C57BL Muscle Fibers, Skeletal / drug effects Muscle Proteins / biosynthesis* Muscle Proteins / genetics Muscle, Skeletal / drug effects* Muscle, Skeletal / pathology Myoblasts / drug effects Myostatin / biosynthesis* Myostatin / genetics Nephrectomy Organ Size / drug effects Organic Anion Transporters / antagonists & inhibitors Oxidative Stress / drug effects* Phosphorylation / drug effects Protein Processing, Post-Translational / drug effects Proto-Oncogene Proteins c-akt / metabolism Receptors, Aryl Hydrocarbon / antagonists & inhibitors SKP Cullin F-Box Protein Ligases / biosynthesis* SKP Cullin F-Box Protein Ligases / genetics Sarcopenia / chemically induced* Sarcopenia / genetics Sarcopenia / metabolism Superoxides / metabolism Uremia / metabolism Uremia / pathology Weight Loss / drug effects |
| IF | 3.998 |
| 引用数 | 32 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |