Background & aims: Dietary regulation is one of the most important factors of intestinal peptide transport. However, the cellular and molecular mechanisms of dietary regulation of the intestinal peptide transport system remain unknown. This study investigated the molecular mechanism of transcriptional activation of intestinal peptide transporter (PepT1) gene by the dietary protein. The promoter region of the rat PepT1 gene was isolated and characterized.
Methods: PepT1 messenger RNA levels were determined by Northern blot analysis. In transient transfection experiments, effects of amino acid and dipeptide on luciferase activity were investigated.
Results: The proximal promoter region of the rat PepT1 gene has a TATA-like box and a GC box sequence. The luciferase activities of the clone -351 RPT-LUC responded to particular 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 selective amino acids and dipeptides in the diet.