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 Gallouzi

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 - 2012
Externally publishedYes

Fingerprint

Cachexia
Nitric Oxide Synthase Type II
ribonucleic acids
muscles
inhibitors
mice
Muscle
nitric oxide
Muscles
dosage
Messenger RNA
Wasting Syndrome
tumors
interferon
acquired immunodeficiency syndrome
Interferons
combat
necrosis
Tumors
Cause of Death

ASJC Scopus subject areas

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

Cite this

The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice. / Di Marco, Sergio; Cammas, Anne; Lian, Xian Jin; Kovacs, Erzsebet Nagy; Ma, Jennifer F.; Hall, Derek T.; Mazroui, Rachid; Richardson, John; Pelletier, Jerry; Gallouzi, Imed.

In: Nature Communications, Vol. 3, 896, 2012.

Research output: Contribution to journalArticle

Di Marco, S, Cammas, A, Lian, XJ, Kovacs, EN, Ma, JF, Hall, DT, Mazroui, R, Richardson, J, Pelletier, J & Gallouzi, I 2012, 'The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice', Nature Communications, vol. 3, 896. https://doi.org/10.1038/ncomms1899
Di Marco, Sergio ; Cammas, Anne ; Lian, Xian Jin ; Kovacs, Erzsebet Nagy ; Ma, Jennifer F. ; Hall, Derek T. ; Mazroui, Rachid ; Richardson, John ; Pelletier, Jerry ; Gallouzi, Imed. / The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice. In: Nature Communications. 2012 ; Vol. 3.
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