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Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells
Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
Viral Hepatitis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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; in revised form: 20 September 2011 / Accepted: 23 September 2011 / Published: 10 October 2011
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
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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.
Prasansuklab A, Poovorawan Y, Tencomnao T. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells. International Journal of Molecular Sciences. 2011; 12(10):6619-6634.
Prasansuklab, Anchalee; Poovorawan, Yong; Tencomnao, Tewin. 2011. "Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells." Int. J. Mol. Sci. 12, no. 10: 6619-6634.