Ouabain exacerbates botulinum neurotoxin-induced muscle paralysis via progression of muscle atrophy in mice
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概要
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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.
- 日本トキシコロジー学会の論文
- 2010-12-01
著者
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ISHII Toshiaki
Department of Molecular Physiology and Biochemistry, Research Institute for Advanced Science and Tec
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Unno Toshihiro
Department Of Pathogenic Veterinary Science United Graduate School Of Veterinary Science Gifu Univer
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Ishii Toshiaki
Department Of Cardiology Surugadai-nihon University Hospital
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Fujikawa Ryu
Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gi
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Muroi Yoshikage
Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gi
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Unno Toshihiro
Department Of Pathogenetic Veterinary Science The United Graduate School Of Veterinary Sciences Gifu
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Fujikawa Ryu
Department Of Pathogenetic Veterinary Science The United Graduate School Of Veterinary Sciences Gifu
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Muroi Yoshikage
Department Of Pathogenetic Veterinary Science The United Graduate School Of Veterinary Sciences Gifu
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Ishii Toshiaki
Department Of Pathogenetic Veterinary Science The United Graduate School Of Veterinary Sciences Gifu
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Muroi Yoshikage
Department of Pathobiological Science, Obihiro University of Agriculture and Veterinary Medicine
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