Negamycin Restores Dystrophin Expression in Skeletal and Cardiac Muscles of mdx Mice

Masayuki Arakawa, Masataka Shiozuka, Yuki Nakayama, Takahiko Hara, Masa Hamada, Shin'ichi Kondo, Daishiro Ikeda, Yoshikazu Takahashi, Ryuichi Sawa, Yoshiaki Nonomura, Kianoush Sheykholeslami, Kenji Kondo, Kimitaka Kaga, Toshio Kitamura, Yuko Suzuki-Miyagoe, Shin'ichi Takeda, Ryoichi Matsuda

研究成果: ジャーナルへの寄稿学術誌査読

94 被引用数 (Scopus)

抄録

The ability of aminoglycoside antibiotics to promote read-through of nonsense mutations has attracted interest in these drugs as potential therapeutic agents in genetic diseases. However, the toxicity of aminoglycoside antibiotics may result in severe side effects during long-term treatment. In this paper, we report that negamycin, a dipeptide antibiotic, also restores dystrophin expression in skeletal and cardiac muscles of the mdx mouse, an animal model of Duchenne muscular dystrophy (DMD) with a nonsense mutation in the dystrophin gene, and in cultured mdx myotubes. Dystrophin expression was confirmed by immunohistochemistry and immunoblotting. We also compared the toxicity of negamycin and gentamicin, and found negamycin to be less toxic. Furthermore, we demonstrate that negamycin binds to a partial sequence of the eukaryotic rRNA-decoding A-site. We conclude that negamycin is a promising new therapeutic candidate for DMD and other genetic diseases caused by nonsense mutations.

本文言語英語
ページ(範囲)751-758
ページ数8
ジャーナルJournal of biochemistry
134
5
DOI
出版ステータス出版済み - 11月 2003

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学

フィンガープリント

「Negamycin Restores Dystrophin Expression in Skeletal and Cardiac Muscles of mdx Mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル