Dexamethasone-Induced Down-Regulation of Nerve Growth Factor Receptor p75NTR is Mediated by Glucocorticoid Type II Receptor in PC12 Cell Model
Shimon Lecht1, Hadar Arien-Zakay1, Rinat Tabakman2, Hao Jiang3, Donald W. Fink4, Philip Lazarovic1, *
Identifiers and Pagination:Year: 2007
First Page: 19
Last Page: 26
Publisher Id: TOPHARMJ-1-19
Article History:Received Date: 12/10/2007
Revision Received Date: 23/10/2007
Acceptance Date: 24/10/2007
Electronic publication date: 7/11/2007
Collection year: 2007
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PC12 clones are established neuronal models to investigate mechanisms involved in the cross-talk between the neurotrophins and drugs. Chronic treatment of PC12 cells with the glucocorticoid agonist drug, dexamethasone (Dex), elicited a 50% decrease in the selective binding of 125I-NGF along with a reduction in the NGF receptor p75NTR mRNA and protein levels, suggesting a transcriptional mechanism. This down regulation of p75NTR was antagonized by the glucocorticoid type II receptor (GR-2), RU-38486 but not by the minerallocorticoid receptor, RU-28318, antagonists. This process was associated with increased autophosphorylation of the NGF receptor, TrkA. Chronic treatment of PC12 with Dex abolished the NGF-induced proliferation of the cells after 20 hours and inhibited by 45% the neurite elongation after 96 hours. RU-38486 blocked Dex-induced shift of PC12 cells from dopaminergic to noradrenergic phenotype. Dexinduced down regulation of p75NTR receptor is mediated by GR-2 and is correlated with disruption of NGF induced proliferation and differentiation. This study may prove relevant with respect to the understanding of neuronal side-effects of corticosteroids.