NF-
B-Induced Loss of MyoD Messenger RNA: Possible Role in Muscle Decay and Cachexia
Denis C. Guttridge,1
Marty W. Mayo,1
Lee
V. Madrid,12
Cun-Yu Wang,1*
Albert S. Baldwin
Jr.123
MyoD regulates skeletal muscle differentiation (SMD) and is
essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-
B) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-B in cytokine-induced muscle
degeneration was explored. In differentiating C2C12 myocytes,
TNF-induced activation of NF-B inhibited SMD by suppressing MyoD
mRNA at the posttranscriptional level. In contrast, in differentiated
myotubes, TNF plus interferon-
(IFN-) signaling was required for
NF-B-dependent down-regulation of MyoD and dysfunction of
skeletal myofibers. MyoD mRNA was also down-regulated by TNF and
IFN- expression in mouse muscle in vivo. These data elucidate a
possible mechanism that may underlie the skeletal muscle decay in
cachexia.
1 Lineberger Comprehensive Cancer Center,
2 Curriculum in Genetics and Molecular Biology,
3 Department of Biology, University of North
Carolina, Chapel Hill, Mason Farm Road, Campus Box 7295, Chapel Hill,
NC, 27599-7295, USA.
*
Present address: Laboratory of Molecular Signaling, Department
of Biologic and Material Science, University of Michigan, Ann Arbor, MI
48109, USA.
To whom correspondence should be addressed. E-mail:
jhall{at}med.unc.edu
