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ID 111610
Title Alternative
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
Author
Sakashita, Yoshihiro Tokushima University
Kitahata, Kanako Tokushima University
Yamashita, Yui Tokushima University
Tomida, Chisato Tokushima University
Kimori, Yuki Tokushima University
Komatsu, Akio Tokushima University
Hirasaka, Katsuya Tokushima University|Nagasaki University KAKEN Search Researchers
Ohno, Ayako Tokushima University
Nakao, Reiko Tokushima University|National Institute of Advanced Industrial Science and Technology Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Higashitani, Atsushi Tohoku University
Higashibata, Akira Japan Aerospace Exploration Agency
Ishioka, Noriaki Japan Aerospace Exploration Agency
Shimazu, Toru Japan Space Forum
Kobayashi, Takeshi Nagoya University
Okumura, Yuushi Tokushima University|Sagami Women’s University KAKEN Search Researchers
Choi, Inho Yonsei University
Oarada, Motoko Sagami Women’s University
Mills, Edward M. University of Texas
Teshima-Kondo, Shigetada Tokushima University|Osaka Prefecture University KAKEN Search Researchers
Takeda, Shin'ichi National Center of Neurology and Psychiatry
Tanaka, Keiji Tokyo Metropolitan Institute of Medical Science
Sokabe, Masahiro Nagoya University
Keywords
Egr
ROS
rat L6 cells
ubquitin ligase Cbl-b
unloading-mediated muscle atrophy
Content Type
Thesis or Dissertation
Description
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.
Journal Title
The American Journal of Physiology. Cell Physiology
ISSN
03636143
15221563
NCID
AA00521122
Publisher
The American Physiological Society
Volume
314
Issue
6
Start Page
C721
End Page
C731
Published Date
2018-06-01
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Takayuki Uchidaの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3146号
Diploma Number
甲栄第255号
Granted Date
2018-03-23
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences
Oral Sciences