Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

International Journal of Molecular Sciences

Anchalee Prasansuklab¹  Yong Poovorawan² 

[1] Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand; E-Mail:;Viral Hepatitis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; E-Mail:

关键词: serotonin transporter;    allelic variation;    transcriptional regulation;    promoter;    hormonal effect;    gastrointestinal tract cells;   

DOI  :  10.3390/ijms12106619

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.