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

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)751-758
Number of pages8
JournalJournal of biochemistry
Issue number5
Publication statusPublished - Nov 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine


Dive into the research topics of 'Negamycin Restores Dystrophin Expression in Skeletal and Cardiac Muscles of mdx Mice'. Together they form a unique fingerprint.

Cite this