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TRAF2 expression in differentiated muscle
1Department of Pathology, Sbarro Institute for Cancer Research and Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
Recent data involving traf2 knockout mice have suggested a necessity of the protein in viability of skeletal muscle tissue. traf2 -/- mice are born with decreased muscle mass that is hypothesized to be due to the increased circulating tumor necrosis factor in these mice. We show that TRAF2 protein is present at high levels in terminally differentiated skeletal muscle in the developing mouse. In vitro differentiation of mouse myoblasts displays a dramatic increase in TRAF2 protein levels. Although basal NF-kappaB activity decreases during myogenesis, TNF-induced NF-kappaB activity is 10 times greater in myotubes compared with myoblasts, presumably because of the stockpiling of TRAF2 protein in these cells. This may represent a strong anti-apoptotic TRAF2-mediated response specifically tailored to myotubes. These data help explain why muscle integrity is at risk in traf2 -/- mice.
Insights
Tumor necrosis factor receptor-associated factor 2 (TRAF2) protein is crucial for skeletal muscle integrity. TRAF2 stockpiling in differentiated muscle cells enhances anti-apoptotic responses, explaining muscle loss in TRAF2-deficient mice.
Area of Science:
- Muscle biology
- Cellular signaling
- Immunology
Background:
- Tumor necrosis factor receptor-associated factor 2 (TRAF2) deficiency in mice leads to reduced skeletal muscle mass.
- This muscle deficit is hypothesized to result from elevated circulating tumor necrosis factor (TNF).
- TRAF2 plays a known role in TNF signaling pathways.
Purpose of the Study:
- To investigate the role and expression of TRAF2 during skeletal muscle differentiation.
- To elucidate the functional significance of TRAF2 in mature muscle cells.
- To understand the molecular basis for muscle integrity defects in TRAF2 knockout models.
Main Methods:
- Analysis of TRAF2 protein levels in developing mouse skeletal muscle.
- In vitro differentiation of mouse myoblasts to myotubes.
- Assessment of basal and TNF-induced NF-kappaB activity in myoblasts and myotubes.
Main Results:
- TRAF2 protein is highly expressed in terminally differentiated skeletal muscle.
- TRAF2 protein levels significantly increase during in vitro myoblast differentiation.
- TNF-induced NF-kappaB activity is markedly enhanced in myotubes compared to myoblasts due to TRAF2 accumulation.
- NF-kappaB activity in myotubes suggests a potent, TRAF2-dependent anti-apoptotic mechanism.
Conclusions:
- TRAF2 protein is upregulated and functionally important in differentiated skeletal muscle.
- Accumulation of TRAF2 in myotubes enhances TNF-induced NF-kappaB signaling, providing an anti-apoptotic effect.
- These findings provide a molecular explanation for the skeletal muscle defects observed in traf2 knockout mice.