These two authors equally contributed to the work.
Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity
Article first published online: 28 SEP 2012
© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 6, pages 963–970, December 2012
How to Cite
J. Neurochem. (2012) 123, 963–970.
- Issue published online: 4 DEC 2012
- Article first published online: 28 SEP 2012
- Accepted manuscript online: 7 SEP 2012 06:10AM EST
- Manuscript Accepted: 1 SEP 2012
- Manuscript Revised: 29 AUG 2012
- Manuscript Received: 27 JUL 2012
- Fondi di Ateneo
- Second University of Naples
- Grant-in-Aid for Scientific Research(C). Grant Number: 16591170
- neural cells;
- REST ;
Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain. Following TPH2 discovery, it was reported that polymorphisms of both gene and non-coding regions are associated with a spectrum of psychiatric disorders. Thus, insights into the mechanisms that specifically regulate TPH2 expression and its modulation by exogenous stimuli may represent a new therapeutic approach to modify serotonergic neurotransmission. To this aim, a CNS-originated cell line expressing TPH2 endogenously represents a valid model system. In this study, we report that TPH2 transcript and protein are modulated by neuronal differentiation in the cell line A1 mes-c-myc (A1). Moreover, we show luciferase activity driven by the human TPH2 promoter region and demonstrate that upon mutation of the NRSF/REST responsive element, the promoter activity strongly increases with cell differentiation. Our data suggest that A1 cells could represent a model system, allowing an insight into the mechanisms of regulation of TPH2 and to identify novel therapeutic targets in the development of drugs for the management of psychiatric disorders.