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Titolo:
SUBSTRATE UP-REGULATION OF THE HUMAN SMALL-INTESTINAL PEPTIDE TRANSPORTER, HPEPT1
Autore:
WALKER D; THWAITES DT; SIMMONS NL; GILBERT HJ; HIRST BH;
Indirizzi:
UNIV NEWCASTLE UPON TYNE,SCH MED,DEPT PHYSIOL SCI NEWCASTLE TYNE NE2 4HH TYNE & WEAR ENGLAND UNIV NEWCASTLE UPON TYNE,DEPT BIOL & NUTR SCI NEWCASTLE TYNE NE2 4HH TYNE & WEAR ENGLAND
Titolo Testata:
Journal of physiology
fascicolo: 3, volume: 507, anno: 1998,
pagine: 697 - 706
SICI:
0022-3751(1998)507:3<697:SUOTHS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-LINE CACO-2; DIPEPTIDE GLYCYLSARCOSINE TRANSPORT; BETA-LACTAM ANTIBIOTICS; RNA-BINDING PROTEIN; MESSENGER-RNA; H+/PEPTIDE COTRANSPORTER; DIETARY CARBOHYDRATE; EXPRESSION CLONING; SUCRASE-ISOMALTASE; GENE-EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
D. Walker et al., "SUBSTRATE UP-REGULATION OF THE HUMAN SMALL-INTESTINAL PEPTIDE TRANSPORTER, HPEPT1", Journal of physiology, 507(3), 1998, pp. 697-706

Abstract

1. Molecular mechanisms underlying physiological adaptation to increased levels of dietary peptides have been elucidated by studying the response to the substrate glycyl-L-glutamine (Gly-Gln) of the proton-coupled peptide transporter, hPepT1, in the Caco-2 human intestinal cell line. V-max for apical uptake of [C-14]glycyl-[C-14]sarcosine was increased 1.64 (+/-0.34)-fold after incubation of Caco-2 cells for 3 days in a peptide-rich medium (4 mM Gly-Gln replacing 4 mM Gln). 2. A full-length Caco-2 hPepT1 cDNA clone was identical to human small intestinal hPepT1 with the exception of a single amino acid substitution Ile-662 to Val. Transcript sizes, on Northern blots of Caco-2 poly(A)(+) RNAprobed with a 630 bp 5' hPepT1 cDNA probe, correspond to the reportedband pattern seen with human small intestinal RNA. The dipeptide-induced increase in substrate transport was accompanied by a parallel increase of 1.92 (+/- 0.30)-fold (n = 9) in hPepT1 mRNA. This was in part due to an increase in hPepT1 mRNA half-life from 8.9 +/- 1.1 to 12.5 +/- 1.6 h (n = 3), but the increase in half-life does not account fullyfor the observed increase in mRNA levels, suggesting that there was also a dipeptide-mediated increase in hPepT1 transcription. 3. Anti-hPepT1-specific antipeptide antibodies localized hPepT1 exclusively to the apical membrane of human small intestinal enterocytes and Caco-2 cells. Gly-Gln supplementation of media resulted in a 1.72 (+/- 0.26)-fold (n = 5) increase in staining intensity of Caco-2 cells. 4. We conclude that Caco-2 cells provide an appropriate model for the study of adaptation of intestinal hPepT1, at the molecular level, to increased levels of dietary peptide. The magnitude of functional increase in apicalpeptide transport activity in response to Gly-Gln can be fully accounted for by the increased levels of hPepT1 protein and mRNA, the lattermediated by both enhanced hPepT1 mRNA stability and increased transcription. The signalling pathway between increased dietary peptide and hPepT1 upregulation, therefore, involves direct action on the enterocyte, independent of hormonal and/or neural control.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:58:45