2. Academic Validation
  3. Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice

Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice

  • J Biochem. 2003 Nov;134(5):751-8. doi: 10.1093/jb/mvg203.
Masayuki Arakawa 1,  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
Affiliations

Affiliation

  • 1 Department of Life Sciences, The University of Tokyo, 3-8-1 Komaba, Tokyo 153-8902.
PMID: 14688241 DOI: 10.1093/jb/mvg203
Abstract

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.

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