The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice

Sergio Di Marco, Anne Cammas, Xian Jin Lian, Erzsebet Nagy Kovacs, Jennifer F. Ma, Derek T. Hall, Rachid Mazroui, John Richardson, Jerry Pelletier, Imed Eddine Gallouzi

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Abstract

Cachexia, or muscle-wasting syndrome, is one of the major causes of death in patients affected by diseases such as cancer, AIDS and sepsis. However, no effective anti-cachectic treatment is currently available. Here we show that a low dose of pateamine A, an inhibitor of translation initiation, prevents muscle wasting caused by the cytokines interferon γ and tumour necrosis factor α or by C26-adenocarcinoma tumours. Surprisingly, although high doses of pateamine A abrogate general translation, low doses selectively inhibit the expression of pro-cachectic factors such as inducible nitric oxide synthase. This selectivity depends on the 5′UTR of inducible nitric oxide synthase messenger RNA (mRNA) that, unlike the 5′UTR of MyoD mRNA, promotes the recruitment of inducible nitric oxide synthase mRNA to stress granules, where its translation is repressed. Collectively, our data provide a proof of principle that nontoxic doses of compounds such as pateamine A could be used as novel drugs to combat cachexia-induced muscle wasting.

Original languageEnglish
Article number896
JournalNature communications
Volume3
DOIs
Publication statusPublished - 1 Jan 2012

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Di Marco, S., Cammas, A., Lian, X. J., Kovacs, E. N., Ma, J. F., Hall, D. T., Mazroui, R., Richardson, J., Pelletier, J., & Gallouzi, I. E. (2012). The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice. Nature communications, 3, [896]. https://doi.org/10.1038/ncomms1899