Abstract | BACKGROUND & AIMS: METHODS: In vitro degradation by PEP of 3H-labeled gliadin peptides 56-88 (33-mer) and 31-49, was analyzed by radio-reverse-phase high-performance liquid chromatography and mass spectrometry. For ex vivo studies, PEP and 3H-peptides were added together onto the mucosal side of duodenal biopsy specimens mounted in Ussing chambers, and peptide transport and digestion were assessed by radio-reverse-phase high-performance liquid chromatography. RESULTS:
Gliadin peptides were degraded partly by 20 mU/mL PEP both in vitro and ex vivo. This concentration of PEP decreased the amount of intact peptides 31-49 and 56-88 crossing the intestinal biopsy specimens of celiac disease patients, but could not prevent the intestinal passage of toxic or immunostimulatory metabolites. PEP concentrations of at least 500 mU/mL for 3 hours were required to achieve full detoxification of peptides and to prevent intestinal transport of active fragments. CONCLUSIONS: After prolonged exposure to high concentrations of PEP, the amount of immunostimulatory gliadin peptides reaching the local immune system in celiac patients is decreased. These results provide a basis to establish whether such conditions are achievable in vivo.
|
Authors | Tamara Matysiak-Budnik, Celine Candalh, Christophe Cellier, Christophe Dugave, Abdelkader Namane, Teresita Vidal-Martinez, Nadine Cerf-Bensussan, Martine Heyman |
Journal | Gastroenterology
(Gastroenterology)
Vol. 129
Issue 3
Pg. 786-96
(Sep 2005)
ISSN: 0016-5085 [Print] United States |
PMID | 16143118
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
Chemical References |
- Oligopeptides
- Tritium
- Gliadin
- Serine Endopeptidases
- Prolyl Oligopeptidases
|
Topics |
- Biopsy
- Celiac Disease
(drug therapy, pathology)
- Chromatography, High Pressure Liquid
- Gliadin
(pharmacokinetics, toxicity)
- Inactivation, Metabolic
- Isotope Labeling
- Mass Spectrometry
- Oligopeptides
(pharmacokinetics)
- Prolyl Oligopeptidases
- Serine Endopeptidases
(therapeutic use)
- Tritium
|