Nandrolone-induced nuclear accumulation of MyoD protein is mediated by Numb, a Notch inhibitor, in C2C12 myoblasts

Physiol Rep, 2018 · DOI: 10.14814/phy2.13520 · Published: January 1, 2018

Simple Explanation

This study investigates how nandrolone, an anabolic steroid, affects muscle cell differentiation, focusing on the roles of MyoD and Numb. It explores how nandrolone influences the expression and location of MyoD, a key protein in muscle development. The research shows that nandrolone increases MyoD production and its movement into the cell nucleus, a process facilitated by Numb. This interaction is crucial for muscle cell differentiation. The findings suggest that nandrolone's effects on muscle development are partly mediated by Numb, which helps MyoD accumulate in the nucleus and bind to specific DNA regions.

Study Duration

Not specified

Participants

C2C12 myoblasts

Evidence Level

Not specified

Key Findings

1
Nandrolone increases both MyoD mRNA and protein expression in C2C12 myoblasts, indicating an upregulation of MyoD production.
2
Nandrolone significantly enhances the nuclear translocation of MyoD protein, suggesting it promotes MyoD's movement into the cell nucleus.
3
Numb knockdown abolishes nandrolone-induced accumulation of MyoD protein, demonstrating Numb's necessity for MyoD nuclear translocation.

Research Summary

This study elucidates the mechanisms by which nandrolone stimulates the differentiation of myogenic lineage cells, focusing on the roles of MyoD and Numb. The research demonstrates that androgens stimulate nuclear translocation of MyoD, forming a complex with Numb, and require Numb for this process. The findings suggest that Numb regulates MyoD's transcriptional activity by tethering to chromatin-bound MyoD, impacting the repertoire and activity of coregulators.

Practical Implications

Muscle Development Therapies

The findings provide novel insights into the mechanisms of muscle development and could inform the development of therapies for muscle-wasting conditions.

Anabolic Steroid Mechanisms

Understanding the interaction between nandrolone, MyoD, and Numb can help to better understand the molecular mechanisms of anabolic steroids.

Numb's Role in Cell Fate

The study highlights the role of Numb in cell fate commitment and myogenic differentiation, which may have implications for regenerative medicine.

Study Limitations

1
The study is performed in vitro using C2C12 myoblasts, which may not fully replicate the complexity of in vivo conditions.
2
The precise mechanisms by which Numb facilitates MyoD nuclear translocation require further investigation.
3
The study focuses on nandrolone; other androgens may have different effects on MyoD and Numb interactions.

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