Int. J. Mol. Sci. 2011, 12(10), 6619-6634; doi:10.3390/ijms12106619
Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells
1
Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
2
Viral Hepatitis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
3
Center for Excellence in Omics-Nano Medical Technology Development Project, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
*
Author to whom correspondence should be addressed.
Received: 16 August 2011 / Revised: 20 September 2011 / Accepted: 23 September 2011 / Published: 10 October 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Abstract
Serotonin (5-HT) is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT) plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR). It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR), lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L) allele as compared to short (S) allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05) as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.Keywords:
serotonin transporter; allelic variation; transcriptional regulation; promoter; hormonal effect; gastrointestinal tract cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Prasansuklab, A.; Poovorawan, Y.; Tencomnao, T. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells. Int. J. Mol. Sci. 2011, 12, 6619-6634.
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