Effects of JBP485 on the expression and function of PEPT1 in indomethacin-induced intestinal injury in rats and damage in Caco-2 cells

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2011-05, Vol.32 (5), p.946-955
• Main Authors: Wang, Wei, Liu, Qi, Wang, Changyuan, Meng, Qiang, Kaku, Taiichi, Liu, Kexin
• Format: Article
• Language: English
• Subjects: Animals; Attenuation; Biological and medical sciences; Biomedical materials; Blotting, Western; Caco-2 Cells; Chromatography, Liquid; Damage; Dipeptide; Dipeptides - metabolism; Expression; Fundamental and applied biological sciences. Psychology; gene expression regulation; human cell lines; Humans; In Vitro Techniques; In vivo testing; Indomethacin; Indomethacin - pharmacology; Injuries; Intestines; Intestines - drug effects; Intestines - injuries; Intestines - metabolism; JBP485; Lipid Peroxidation - drug effects; Male; messenger RNA; oxidative stress; Oxidative Stress - drug effects; PEPT1; Peptide Transporter 1; Peptides, Cyclic - pharmacology; Peroxidase - metabolism; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Symporters - genetics; Symporters - metabolism; Tandem Mass Spectrometry; Uptakes; Vertebrates: endocrinology; Western blotting
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2011.01.031

► Indomethacin causes injury in rat intestine and damage in Caco-2 cells. ► JBP485 is a dipeptide with antihepatitis activity, was first isolated from Laennec. ► JBP485 reverses indomethacin-induced injury by reducing oxidative stress. ► JBP485 partially blocks indomethacin-induced down-regulation of PEPT1. To investigate the effect of JBP485 (an anti-inflammatory dipeptide) on PEPT1 in indomethacin-induced intestinal injury in rats and damage in Caco-2 cells, the activity and expression of PEPT1 were examined. The effects of treatment with indomethacin and co-treatment with JBP485 were examined in terms of intestinal histological changes, MDA and MPO levels in rats; as well as LDH-release and oxidative stress in Caco-2 cells. Uptake of glycylsarcosine (Gly-Sar) by PEPT1 was determined by in vivo, in vitro and in situ studies. RT-PCR and Western blot were used to assess the expression of PEPT1 in rat intestine and Caco-2 cells. JBP485 caused a significant decrease in MDA and MPO levels, and improved the pathological condition of rat intestine, while attenuating Caco-2 cells damage induced by indomethacin. Uptake of Gly-Sar by PEPT1 was decreased by indomethacin treatment, whereas the Gly-Sar plasma concentration was markedly increased in JBP485 co-treated rats. Indomethacin down-regulated the expression of PEPT1 mRNA and protein in rat intestine and Caco-2 cells, and the effects were reversed after administration of JBP485. These results indicated that JBP485 not only improved intestinal injury and cell damage but also partially blocked the down-regulation of PEPT1 expression and function induced by indomethacin.