Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells

• Material Type: 博士論文
• Title: Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells
• Author/Editor: Uchida, Takayuki; Sakashita, Yoshihiro; Kitahata, Kanako; Yamashita, Yui; Tomida, Chisato; Kimori, Yuki; Komatsu, Akio; Hirasaka, Katsuya; Ohno, Ayako; Nakao, Reiko; Higashitani, Atsushi; Higashibata, Akira; Ishioka, Noriaki; Shimazu, Toru; Kobayashi, Takeshi; Okumura, Yuushi; Choi, Inho; Oarada, Motoko; Mills, Edward M.; Teshima-Kondo, Shigetada; Takeda, Shin'ichi; Tanaka, Eiji; Tanaka, Keiji; Sokabe, Masahiro; Nikawa, Takeshi
• Author Heading: Uchida, Takayuki; Sakashita, Yoshihiro; Kitahata, Kanako; Yamashita, Yui; Tomida, Chisato; Kimori, Yuki; Komatsu, Akio; Hirasaka, Katsuya; Ohno, Ayako; Nakao, Reiko; Higashitani, Atsushi; Higashibata, Akira; Ishioka, Noriaki; Shimazu, Toru; Kobayashi, Takeshi; Okumura, Yuushi; Choi, Inho; Oarada, Motoko; Mills, Edward M.; Teshima-Kondo, Shigetada; Takeda, Shin'ichi; Tanaka, Eiji; Tanaka, Keiji; Sokabe, Masahiro; Nikawa, Takeshi
• Publication, Distribution, etc.: The American Physiological Society
• Publication Date: 2018-06-01
• Publication Date (W3CDTF): 2018-06-01
• Alternative Title: 筋萎縮関連ユビキチンリガーゼCbl-bの発現調節における酸化ストレスの重要性; ROS induced Cbl-b expression in rat L6 cells
• Periodical title: The American Journal of Physiology. Cell Physiology
• No. or year of volume/issue: 314 6
• Volume: 314
• Issue: 6
• Pages: C721-C731
• ISSN (Periodical Title): ISSN : 0363-6143; ISSN : 1522-1563
• Degree grantor/type: 徳島大学
• Date Granted: 2018-03-23
• Dissertation Number: 甲第3146号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Subject Heading: Egr; ROS; rat L6 cells; ubquitin ligase Cbl-b; unloading-mediated muscle atrophy
• Target Audience: 一般
• Note (General): Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798–4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at −110 to −60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1152/ajpcell.00184.2017
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

http://repo.lib.tokushima-u.ac.jp/files/public/11/111610/20180515143706627913/k3146_abstract_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/111610/20181212145832644349/k3146_fulltext.pdf fulltext