TNF-alpha increases protein content in C2C12 and primary myotubes by enhancing protein translation via the TNF-R1, PI3K, and MEK

Plaisance, I. and Morandi, C. and Murigande, C. and Brink, M.. (2008) TNF-alpha increases protein content in C2C12 and primary myotubes by enhancing protein translation via the TNF-R1, PI3K, and MEK. American journal of physiology. Endocrinology and metabolism, Vol. 294, H. 2 , E241-250.

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Official URL: http://edoc.unibas.ch/dok/A6006133

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Recent evidence supports that TNF-alpha, long considered a catabolic factor, may also have a physiological function in skeletal muscle. The catabolic view, mainly based on correlative studies in human and in vivo animal models, was challenged by experiments with myoblasts, in which TNF-alpha induced differentiation. The biological effects of TNF-alpha in differentiated muscle, however, remain poorly understood. In the present study, we tested whether TNF-alpha has growth-promoting effects in myotubes, and we characterized the mechanisms leading to these effects. Treatment of C(2)C(12) myotubes with TNF-alpha for 24 h increased protein synthesis (PS) and enhanced cellular dehydrogenase activity by 22 and 26%, respectively, without changing cell numbers. These effects were confirmed in myotubes differentiated from primary rat myoblasts. TNF-alpha activated two signaling cascades: 1) ERK1/2 and its target eIF4E and 2) Akt and its downstream effectors GSK-3, p70(S6K), and 4E-BP1. TNF-alpha-induced phosphorylation of Akt, and ERK1/2 was inhibited by an antibody against TNF-alpha receptor 1 (TNF-R1). PD-98059 pretreatment abolished TNF-alpha-induced phosphorylation of ERK1/2 and eIF4E, whereas PS was only partially inhibited. LY-294002 completely abolished TNF-alpha-induced stimulation of PS as well as phosphorylation of Akt and its downstream targets GSK-3, p70(S6K), and 4E-BP1. Rapamycin inhibited TNF-alpha-induced phosphorylation of the mTOR C1 target p70(S6K) without altering TNF-alpha-induced PS and 4E-BP1 phosphorylation. In conclusion, our results provide evidence that TNF-alpha enhances PS in myotubes and that this is based on enhanced protein translation mediated by the TNF-R1 and PI3K-Akt and MEK-ERK signaling cascades.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > CardioBiology (Brink)
UniBasel Contributors:Brink, Marijke
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Mar 2014 13:13
Deposited On:27 Mar 2014 13:13

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