The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice
Open Access
- 1 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 3 (1), 896
- https://doi.org/10.1038/ncomms1899
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.This publication has 55 references indexed in Scilit:
- Transportin 2 Regulates Apoptosis through the RNA-binding Protein HuRPublished by Elsevier BV ,2011
- Toll‐like receptor 4 mediates lipopolysaccharide‐induced muscle catabolismviacoordinate activation of ubiquitin‐proteasome and autophagy‐lysosome pathwaysThe FASEB Journal, 2010
- ENDOTOXIN AND INTERFERON-γ INHIBIT TRANSLATION IN SKELETAL MUSCLE CELLS BY STIMULATING NITRIC OXIDE SYNTHASE ACTIVITYShock, 2009
- Oxidative Stress Increases the Number of Stress Granules in Senescent Cells and Triggers a Rapid Decrease in p21waf1/cip1 TranslationPublished by Elsevier BV ,2009
- Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patientsBritish Journal of Cancer, 2007
- Cytoplasmic Relocalization of Heterogeneous Nuclear Ribonucleoprotein A1 Controls Translation Initiation of Specific mRNAsMolecular Biology of the Cell, 2007
- Inhibition of the Ubiquitin-Proteasome System Induces Stress Granule FormationMolecular Biology of the Cell, 2007
- Cell stress modulates the function of splicing regulatory protein RBM4 in translation controlProceedings of the National Academy of Sciences of the United States of America, 2007
- Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α PhosphorylationMolecular Biology of the Cell, 2006
- Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4ANature Chemical Biology, 2006