%0 Journal Article
%T Dexamethasone-Induced Down-Regulation of Nerve Growth Factor Receptor p75NTR is Mediated by Glucocorticoid Type II Receptor in PC12 Cell Model
%A Shimon Lecht
%A Hadar Arien-Zakay
%A Rinat Tabakman
%A Hao Jiang
%A Donald W. Fink and Philip Lazarovici
%J The Open Pharmacology Journal
%D 2007
%I 
%R 10.2174/1874143600701010019]
%X 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.
%U http://www.benthamscience.com/open/topharmj/articles/V001/19TOPHARMJ.htm