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Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA
Steroid hormones and growth factors control neuritogenesis through their cognate receptors under physiological and pathological conditions. We have already shown that nerve growth factor and androgens induce neurite outgrowth of PC12 cells through a reciprocal crosstalk between the NGF receptor, Trk...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913450/ https://www.ncbi.nlm.nih.gov/pubmed/36766714 http://dx.doi.org/10.3390/cells12030373 |
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author | Di Donato, Marzia Bilancio, Antonio Auricchio, Ferdinando Castoria, Gabriella Migliaccio, Antimo |
author_facet | Di Donato, Marzia Bilancio, Antonio Auricchio, Ferdinando Castoria, Gabriella Migliaccio, Antimo |
author_sort | Di Donato, Marzia |
collection | PubMed |
description | Steroid hormones and growth factors control neuritogenesis through their cognate receptors under physiological and pathological conditions. We have already shown that nerve growth factor and androgens induce neurite outgrowth of PC12 cells through a reciprocal crosstalk between the NGF receptor, TrkA and the androgen receptor. Here, we report that androgens or NGF induce neuritogenesis in PC12 cells through inactivation of RhoA. Ectopic expression of the dominant negative RhoA N19 promotes, indeed, the neurite-elongation of unchallenged and androgen- or NGF-challenged PC12 cells and the increase in the expression levels of βIII tubulin, a specific neuronal marker. Pharmacological inhibition of the Ser/Thr kinase ROCK, an RhoA effector, induces neuritogenesis in unchallenged PC12 cells, and potentiates the effect of androgens and NGF, confirming the role of RhoA/ROCK axis in the neuritogenesis induced by androgen and NGF, through the phosphorylation of Akt. These findings suggest that therapies based on new selective androgen receptor modulators and/or RhoA/ROCK inhibitors might exert beneficial effects in the treatment of neuro-disorders, neurological diseases and ageing-related processes. |
format | Online Article Text |
id | pubmed-9913450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99134502023-02-11 Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA Di Donato, Marzia Bilancio, Antonio Auricchio, Ferdinando Castoria, Gabriella Migliaccio, Antimo Cells Article Steroid hormones and growth factors control neuritogenesis through their cognate receptors under physiological and pathological conditions. We have already shown that nerve growth factor and androgens induce neurite outgrowth of PC12 cells through a reciprocal crosstalk between the NGF receptor, TrkA and the androgen receptor. Here, we report that androgens or NGF induce neuritogenesis in PC12 cells through inactivation of RhoA. Ectopic expression of the dominant negative RhoA N19 promotes, indeed, the neurite-elongation of unchallenged and androgen- or NGF-challenged PC12 cells and the increase in the expression levels of βIII tubulin, a specific neuronal marker. Pharmacological inhibition of the Ser/Thr kinase ROCK, an RhoA effector, induces neuritogenesis in unchallenged PC12 cells, and potentiates the effect of androgens and NGF, confirming the role of RhoA/ROCK axis in the neuritogenesis induced by androgen and NGF, through the phosphorylation of Akt. These findings suggest that therapies based on new selective androgen receptor modulators and/or RhoA/ROCK inhibitors might exert beneficial effects in the treatment of neuro-disorders, neurological diseases and ageing-related processes. MDPI 2023-01-19 /pmc/articles/PMC9913450/ /pubmed/36766714 http://dx.doi.org/10.3390/cells12030373 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Donato, Marzia Bilancio, Antonio Auricchio, Ferdinando Castoria, Gabriella Migliaccio, Antimo Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title | Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title_full | Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title_fullStr | Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title_full_unstemmed | Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title_short | Androgens and NGF Mediate the Neurite-Outgrowth through Inactivation of RhoA |
title_sort | androgens and ngf mediate the neurite-outgrowth through inactivation of rhoa |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913450/ https://www.ncbi.nlm.nih.gov/pubmed/36766714 http://dx.doi.org/10.3390/cells12030373 |
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