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SRC-1 is involved in the control of the gene expression of myelin protein po

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Abstract

Steroid receptor coactivator-1 (SRC-1) has a crucial role in many different biological effects mediated by nuclear receptors. However, in spite of its ubiquitous expression, there are no data regarding its possible involvement in nuclear receptor transcriptional activity at the level of the peripheral nervous system. We investigated whether this coactivator might have a role in the control of glycoprotein Po gene expression. This myelin protein is a specific product of Schwann cells, with a fundamental role in the maintenance and functionality of peripheral myelin. Po is known to be stimulated by progesterone and by its 5α-reduced metabolite, dihydroprogesterone (DHP), through the corresponding steroid receptor. To determine whether the effect exerted by DHP on Po mRNA levels could be affected by and therefore associated with altered levels of SRC-1, a mouse Schwann cell line was stably transfected to over- or underexpress this coactivator. We found that SRC-1 overexpressing cells are more responsive to Po mRNA induction by DHP, whereas the effect of the steroid is completely lost in SRC-1-deficient cells. Interestingly, SRC-1 levels are also positively correlated with Po gene expression independently of DHP exposure. Finally, DHP treatment increases not only Po but also SRC-1 mRNA levels. Altogether, these data indicate for the first time that in rat Schwann cells, SRC-1 plays a role in the regulation of one of the most typical proteins of peripheral myelin.

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Authors and Affiliations

  1. Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133, Milan, Italy

    Ilaria Teresa Rita Cavarretta, Luciano Martini, Marcella Motta & Roberto Cosimo Melcangi

  2. Department of Urology, University of Innsbruck, 6020, Innsbruck, Austria

    Ilaria Teresa Rita Cavarretta

  3. Department of Molecular and Cell Biology, Baylor College of Medicine, 77030, Houston, TX

    Carolyn Louise Smith

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  1. Ilaria Teresa Rita Cavarretta
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  2. Luciano Martini
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  3. Marcella Motta
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  4. Carolyn Louise Smith
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  5. Roberto Cosimo Melcangi
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Correspondence to Roberto Cosimo Melcangi.

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Cavarretta, I.T.R., Martini, L., Motta, M. et al. SRC-1 is involved in the control of the gene expression of myelin protein po. J Mol Neurosci 24, 217–226 (2004). https://doi.org/10.1385/JMN:24:2:217

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  • DOI: https://doi.org/10.1385/JMN:24:2:217

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