Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers

Foster, David R.; Landowski, Christopher P.; Zheng, Xiaomei; Amidon, Gordon L.; Welage, Lynda S.

doi:10.1016/j.phrs.2008.11.001

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Inflammatory bowel disease and diet also have distinct regulatory effects on PepT1. 22−26 Moreover, epidermal growth factor and intracellular Ca 2+ concentration can affect the expression and function of PepT2. 27,28 However, limited information is available on the regulation or mechanism of regulation for PhT1 and PhT2.…”

Section: Discussionmentioning

confidence: 99%

Expression and Regulation of the Proton-Coupled Oligopeptide Transporter PhT2 by LPS in Macrophages and Mouse Spleen

et al. 2014

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Membrane transporter PhT2 (SLC15A3), which belongs to the proton-coupled oligopeptide transporter family, mediates the transport of di/tripeptides and histidine utilizing an inwardly directed proton gradient and negative membrane potential. The aim of this study was to elucidate the molecular expression of PhT2 in macrophages and mouse tissues and to explore the regulation of PhT2 by lipopolysaccharide (LPS). The results showed relatively high expression of PhT2 in J774A.1 and THP-1 macrophage cells, mouse spleen, and lung. Using an LPS-induced inflammatory cell model, we found that hPhT2 mRNA expression was up-regulated in THP-1 cells and that the up-regulation was suppressed by pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB. Similar results were observed in mouse spleen during LPS-induced acute inflammation. Using dual-labeling immunofluorescence and confocal laser scanning microscopy, we confirmed that mPhT2 was colocalizing with lysosome-associated membrane protein 1 in transfected HEK293 cells. These results suggested that PhT2, a lysosomal membrane transporter, was up-regulated by LPS via the NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Expression and Regulation of the Proton-Coupled Oligopeptide Transporter PhT2 by LPS in Macrophages and Mouse Spleen

et al. 2014

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“…Mechanisms involved in the regulation of PepT1 include changes in mRNA and protein expression levels, alterations in transport activity, and modification of protein recruitment to the plasma membrane (29). For example, Vavricka et al (30,31) found that high concentrations of interferon-g and tumor necrosis factor-a increased PepT1-mediated dipeptide uptake in a dose-and time-dependent manner through increased expression of total and apical membrane-localized PepT1 in Caco-2 BBe cells. In addition, long-term treatment with leptin, a hormone secreted by both adipocytes and the stomach, caused a significant increase in dipeptide uptake in ob/ob mice and this effect was associated with increases in expression of the PepT1 mRNA and protein (32).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus plantarum Consumption Increases PepT1-Mediated Amino Acid Absorption by Enhancing Protein Kinase C Activity in Spontaneously Colitic Mice

Chen¹,

Shen²,

Zhou³

et al. 2010

The Journal of Nutrition

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Although probiotic consumption has generally been shown to have many beneficial effects for the prevention and treatment of inflammatory bowel disease, the effects of Lactobacillus plantarum (LP) on intestinal nutrient absorption, particularly oligopeptide transporter 1 (PepT1)-mediated absorption of dietary protein under inflammatory conditions, has not yet been characterized. In this study, we first investigated the effects of LP consumption on plasma amino acid concentrations and PepT1-mediated absorption of cephalexin in the small intestine of wild-type (WT) mice and interleukin-10 knockout (IL-10(-/-)) mice, a model of spontaneous colitis. We then analyzed expression and distribution of PepT1 and protein kinase C (PKC) activity in the jejunum of these mice. LP consumption (10(9) colony-forming units/0.5 mL) delivered by gavage once per day for 4 wk increased the total plasma amino acid concentration and the concentration of plasma cephalexin through enhancement of PepT1-mediated uptake in LP treated IL-10(-/-) mice compared with IL-10(-/-) mice. However, Western blotting and quantitative PCR analysis revealed no significant differences in PepT1 protein and mRNA expression between LP-treated and untreated mice. Additionally, immunofluorescence analysis showed that PepT1 did not appear to be mislocalized in IL-10(-/-) mice. Interestingly, IL-10(-/-) mice had significantly lower PKC activity and expression of phosphorylated PKC compared with WT mice, and these decreases could be prevented by LP treatment. These data suggest that consumption of LP enhances PepT1-mediated amino acid absorption, likely through alterations in PKC activity, as opposed to changes in expression or distribution of PepT1 in the small intestine of IL-10(-/-) mice.

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“…Unlike the glucose transport system of SGLT1 and GLUT2, stereospecificity cannot be exploited, and thus, differentially radio-labeled stereoisomers cannot be used. Reports in the literature are not unanimous and employ typically one of three methods to correct total uptake for passive uptake in the study of PepT1-mediated transport: 1) perform the experiment at near-freezing temperatures in order to “inactivate” the transporter (20, 21), 2) inhibit competitively the uptake of the compound of interest with a markedly greater concentration of a second substrate for which the transporter has a greater affinity (lesser K m ) (2, 6, 15, 22-24), and 3) use nonlinear regression analysis of total uptake with modified Michaelis-Menten kinetics (1, 6, 25-28). Because PepT1 relies on a proton gradient and functions most efficiently at a pH of 6.0, we hypothesized that passive uptake might also be estimated by increasing the pH of test solutions to a pH of 8.0 (29).…”

Section: Introductionmentioning

confidence: 99%

“…We devised a study using Caco-2 cells and the model dipeptide glycyl-sarcosine (gly-sar). The Caco-2 cell line is a well-characterized, human-derived, cell culture model of intestinal epithelium known to express PepT1; Caco-2 cells are used frequently in studies of nutrient absorption and pharmacokinetics (1-3, 6, 14, 15, 20-22, 24-28, 30-32). Gly-Sar is a model, hydrolysis-resistant dipeptide not found in nature and is used frequently as a substrate to study PepT1-mediated transport (13).…”

Section: Introductionmentioning

confidence: 99%

Differentiating Passive from Transporter-Mediated Uptake by PepT1: A Comparison and Evaluation of Four Methods

Scow

Madhavan

Chaudhry

et al. 2011

Journal of Surgical Research

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Introduction-To quantify transmembrane transport of dipeptides by PepT1, passive uptake (non-PepT1 mediated) must be subtracted from total (measured) uptake. Three methods have been described to estimate passive uptake: perform experiments at cold temperatures, inhibit target dipeptide uptake with greater concentration of a second dipeptide, or use modified MichaelisMenten kinetics. We hypothesized that performing uptake experiments at pH (8.0) would estimate passive uptake accurately, because PepT1 requires a proton gradient. Our aim was to determine the most accurate method to estimate passive uptake.

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Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers

Cited by 13 publications

References 35 publications

Expression and Regulation of the Proton-Coupled Oligopeptide Transporter PhT2 by LPS in Macrophages and Mouse Spleen

Expression and Regulation of the Proton-Coupled Oligopeptide Transporter PhT2 by LPS in Macrophages and Mouse Spleen

Lactobacillus plantarum Consumption Increases PepT1-Mediated Amino Acid Absorption by Enhancing Protein Kinase C Activity in Spontaneously Colitic Mice

Differentiating Passive from Transporter-Mediated Uptake by PepT1: A Comparison and Evaluation of Four Methods

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