Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p)-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.
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Authors | Fabio Penna, Domiziana Costamagna, Alessandro Fanzani, Gabriella Bonelli, Francesco M Baccino, Paola Costelli |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 10
Pg. e13604
(Oct 27 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21048967
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Flavonoids
- Protein Kinase Inhibitors
- Extracellular Signal-Regulated MAP Kinases
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- Animals
- Blotting, Western
- Body Weight
- Cell Line
- Enzyme-Linked Immunosorbent Assay
- Extracellular Signal-Regulated MAP Kinases
(antagonists & inhibitors)
- Flavonoids
(pharmacology)
- Fluorescent Antibody Technique
- Male
- Mice
- Mice, Inbred BALB C
- Muscle, Skeletal
(pathology)
- Muscular Atrophy
(pathology)
- Neoplasms, Experimental
(pathology)
- Organ Size
- Protein Kinase Inhibitors
(pharmacology)
- Rats
- Rats, Wistar
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