Cellular and molecular mechanisms of dietary regulation on rat intestinal H+/peptide transporter PepT1

Background & Aims: Dietary regulation is one of the most important factors of intestinal peptide transport. However, the cellular and molecular mechan isms of dietary regulation of the intestinal peptide transport system remai n unknown. This study investigated the molecular mechanism of transcription al activation of intestinal peptide transporter (PepT1) gene by the dietary protein. The promoter region of the rat PepT1 gene was isolated and charac terized. Methods: PepT1 messenger RNA levels were determined by Northern bl ot analysis. In transient transfection experiments, effects of amino acid a nd dipeptide on luciferase activity were investigated. Results: The proxima l promoter region of the rat PepT1 gene has a TATA-like box and a GC box se quence. The luciferase activities of the clone -351 RPT-LUC responded to pa rticular amino acids (phenylalanine, arginine, and lysine) and dipeptides ( Gly-Sar, Gly-Phe, Lys-Phe, and Asp-Lys). An AP-1 binding site and an amino acid-responsible element were present at -295 and -277 nucleotides relative to the transcription start site in this region. Conclusions: These results suggest that the up-regulation of dipeptide transport activity by dietary protein is caused by transcriptional activation of the PepT1 gene by select ive amino acids and dipeptides in the diet.