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タイトル: Ouabain exacerbates botulinum neurotoxin-induced muscle paralysis via progression of muscle atrophy in mice
著者: Fujikawa, Ryu
Muroi, Yoshikage
Unno, Toshihiro
Ishii, Toshiaki
室井, 喜景
石井, 利明
キーワード: Ouabain
Botulinum neurotoxin
Muscle atrophy
MAFbx
MuRF-1
発行日: 2010
出版者: 日本毒性学会
誌名: The Journal of Toxicological Sciences
巻: 35
号: 6
開始ページ: 795-805
抄録: Botulinum neurotoxin serotype A (BoNT/A) inhibits acetylcholine release at the neuromuscular junction in isolated muscles, and ouabain can partially block its effect. However, it is not clear whether ouabain attenuates BoNT/A-induced neuromuscular paralysis in vivo. In this work, we investigated the effects of ouabain on BoNT/A-induced neuromuscular paralysis in mice. Ouabain was administered to mice intraperitoneally immediately after a single injection of BoNT/A into skeletal muscle. The effects of ouabain on BoNT/A-induced muscle paralysis were assessed by quantitative monitoring of muscle tension and digit abduction via the digit abduction scoring (DAS) assay. A single administration of ouabain significantly prolonged BoNT/A-induced neuromuscular paralysis. Moreover, consecutive daily injection of ouabain exacerbated BoNT/A-induced neuromuscular paralysis, and led to a significant decrease in both twitch and tetanic forces as assayed in isolated BoNT/A-injected muscles. We next looked at the effects of ouabain on BoNT/A-induced muscle atrophy. Administration of ouabain led to a decrease in the myofibrillar cross-sectional area (CSAs) by 14 post-BoNT/A injection. In addition, repeated administration of ouabain increased mRNA expression levels of ubiquitin ligases, which are markers of muscle atrophy, in BoNT/A-injected muscle. These results suggest that ouabain exacerbates BoNT/A-induced neuromuscular paralysis via a marked progression of BoNT/A-induced muscle atrophy.
URI: http://ir.obihiro.ac.jp/dspace/handle/10322/3123
ISSN: 1880-3989
0388-1350
権利情報: 日本毒性学会
出現コレクション:00C01学術雑誌論文

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