Functional and molecular expression of intestinal oligopeptide transporter (Pept-1) after a brief fast

Thamotharan, Manikkavasagar; Bawani, Shahab Zare; Zhou, Xiaodong; Adibi, Siamak A.

doi:10.1016/s0026-0495(99)90164-6

Cited by 87 publications

(69 citation statements)

References 14 publications

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“…In a third study (32), it was observed that short-term starvation (4-d fast but free access to water) markedly increased the amount of PEPT1 protein present in rat jejunum, whereas dietary administration of amino acids reduced PEPT1 protein. These results were subsequently confirmed by a preliminary report (33) in which the functional and molecular expression of PEPT1 was upregulated after a brief fast (i.e. 1-d fast but free access to water) in rat jejunal brush border membrane vesicles.…”

supporting

confidence: 74%

Developmental Expression of PEPT1 and PEPT2 in Rat Small Intestine, Colon, and Kidney

2001

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Mammalian peptide transporters (PEPT1 and PEPT2) play a pivotal role in the absorption of small peptides from the intestine and kidney, respectively, and in the disposition and targeting of peptide or mimetic drugs. However, there are few reports on the molecular basis of their regulation, especially in the young. The aim of this study was to determine the developmental expression of intestinal and renal oligopeptide transporters in rats from embryonic to adult ages. Intestinal segments were collected (i.e. duodenum, jejunum, ileum, and colon) along with whole kidney, and their mRNA and protein levels were measured. Expression levels of PEPT1 were maximal 3-5 d after birth in the duodenum, jejunum, and ileum, and then declined rapidly. Expression was increased transiently at d 24, most notably in the ileum. Adult protein levels were approximately 70% of that observed on d 3-5. Significant PEPT1 expression was observed in colon during the first week of life, but levels were undetectable shortly thereafter through adulthood. PEPT1 and PEPT2 expression is less regulated in rat kidney and more pronounced in older animals. Peptide transporters were also present as early as d 20 of fetal life for all tissues tested. These results are unique in providing the developmental expression of peptide transporter mRNA and protein in distinct regions of the small intestine, colon, and kidney in rat. Our findings suggest that intestinal expression of PEPT1 is induced postpartum, possibly by suckling, and again at the time of weaning, and that the colon may participate in peptide transport early in life. Expression and molecular cloning studies have resulted in the identification of two distinct proton-coupled oligopeptide transporters in rabbit (1-3), rat (4 -6), and human (7, 8) (i.e. PEPT1 as low-affinity carrier, PEPT2 as high-affinity carrier). The proteins range in size from 707 to 729 amino acids in various species, with high homology between species for a given transporter (approximately 80%) and less homology between transporters for a given species (approximately 50%). The gene products, as predicted by hydropathy analysis, contain 12 membrane-spanning domains and a large extracellular loop between transmembrane domains 9 and 10. The encoded proteins have a number of potential N-glycosylation as well as protein kinase recognition sites, which suggests that the transporters may be regulated by reversible phosphorylation. More recently, a third peptide transporter, PHT1, was cloned from rat brain (9). Encoding a protein of 572 amino acids, hydropathy analysis predicts the presence of 12 transmembrane domains. There are also multiple N-glycosylation sites in the hydrophilic extracellular loop of PHT1, along with potential sites for protein kinase C-dependent phosphorylation. PHT1 is novel in that it transports histidine, as well as small peptides, with high affinity and in a proton gradient-dependent manner. Although expressed in the brain and eye, PHT1 is not found in the intestine or kidney and shows little homology to P...

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supporting

confidence: 74%

Developmental Expression of PEPT1 and PEPT2 in Rat Small Intestine, Colon, and Kidney

2001

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“…The investigation of mechanism of this increase in transport by analysis of its kinetic constants showed that the K m was unaffected, whereas the V max was increased by twofold, suggesting an increase in the membrane population of Pept-1. This suggestion was verified by the Western blot analysis of Pept-1 located in the brush-border membrane (51). The mechanism of the increase in the population of the transporter appeared to be pretranslational, because fasting increased the gene expression of Pept-1 by severalfold (51).…”

Section: Fastingmentioning

confidence: 87%

“…A common nutritional condition is a brief fast in patients who become acutely ill. With this condition as a model of malnutrition, its effect on functional and molecular expressions of Pept-1 was investigated (51). Rats were fasted for 24 h before the jejunum was removed for the following studies.…”

Section: Fastingmentioning

confidence: 99%

Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease

Adibi

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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194

131

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The abundance of the oligopeptide transporter (Pept-1) in the brush-border membrane of the intestinal epithelium is the central mechanism for regulation of transport of products of protein digestion (dipeptides and tripeptides) and peptidomimetic drugs (for example, β-lactam antibiotics). Within the past few years, there has been substantial progress in identifying the factors controlling this regulation and the mechanisms of their actions. The purpose of this report is to review this progress. The studies of individual substrates and hormones in a human intestinal cell line (Caco-2) have shown that dipeptides, certain amino acids, insulin, and leptin increase and epidermal growth factor and triiodothyronine decrease the membrane population of Pept-1. In the case of dipeptides, epidermal growth factor, and thyroid hormone, there are parallel changes in the gene expression brought about by alteration of transcription and/or stability of Pept-1 mRNA. In contrast, the treatment with insulin and leptin does not induce any alteration in the Pept-1 gene expression, and the mechanism of increased protein expression appears to be increased trafficking from a preformed cytoplasmic pool to the apical membrane. In vivo studies in rats have shown modulation of protein and gene expressions of the intestinal oligopeptide transporter during the day and during development and in nutritional and metabolic alterations, such as high-protein diet, fasting, and diabetes. Patients with intestinal diseases, such as ulcerative colitis, Crohn's disease, and short-bowel syndrome, may have induction of the Pept-1 expression in their colon. Finally, pharmacological studies have shown that the expression of Pept-1 can be upregulated by agents such as 5 fluorouracil and downregulated by agents such as cyclosporine. In conclusion, the above studies have produced a wealth of new information on regulation of a key transporter in the intestine. This information may have useful applications in nutritional and pharmacological treatments, for example, in diabetic patients needing enteral nutrition or in ulcerative colitis patients needing the suppression of the intestinal inflammation.

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“…Caco-2 cells (passages [35][36][37][38][39][40][41][42][43][44][45] were cultured in DMEM supplemented with 20% FBS and 1% nonessential amino acids. Cells were kept at 37°C in 5% CO 2 and 90% humidity.…”

Section: Methodsmentioning

confidence: 99%

PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine

Buyse

Berlioz²,

Guilmeau³

et al. 2001

J. Clin. Invest.

193

163

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Functional and molecular expression of intestinal oligopeptide transporter (Pept-1) after a brief fast

Cited by 87 publications

References 14 publications

Developmental Expression of PEPT1 and PEPT2 in Rat Small Intestine, Colon, and Kidney

Developmental Expression of PEPT1 and PEPT2 in Rat Small Intestine, Colon, and Kidney

Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease

PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine

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