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

Signaling via the androgen receptor (AR) stimulates myogenic progenitor differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb, a Notch inhibitor, play key roles in regulating myogenic differentiation. Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by nandrolone are unclear. Moreover, the potential crosstalk between nandrolone, MyoD, and Numb is not well understood. With these considerations in mind, we examined the effects of nandrolone on the expression of MyoD mRNA and protein, and determined the interactions of MyoD and Numb in the presence or absence of nandrolone in differentiating C2C12 myoblasts. Nandrolone increased MyoD mRNA and protein expression and significantly enhanced nuclear translocation of MyoD protein. The later effect of nandrolone was blunted by siRNA against Numb. Immunoprecipitation (IP) studies confirmed that Numb forms complexes with MyoD. Chromatin IP revealed that in the presence of nandrolone, Numb is recruited to a region of the MyH7 promotor containing the E-box to which MyoD binds. These data indicate that nandrolone-regulated MyoD activation occurs mainly through a posttranslational mechanism which promotes MyoD nuclear accumulation, and suggest that this effect of nandrolone is, at least in part, mediated by Numb. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Citation

Xin-Hua Liu, Rita De Gasperi, William A Bauman, Christopher P Cardozo. Nandrolone-induced nuclear accumulation of MyoD protein is mediated by Numb, a Notch inhibitor, in C2C12 myoblasts. Physiological reports. 2018 Jan;6(1)

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PMID: 29333723

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