Progastrin1–80stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites

التفاصيل البيبلوغرافية
العنوان: Progastrin1–80stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites
المؤلفون: András Varró, Brian T. Miller, Xianbin Lu, Stephanie Cobb, A. Owlia, Nadya Tarasova, Pomila Singh
المصدر: American Journal of Physiology-Gastrointestinal and Liver Physiology. 284:G328-G339
بيانات النشر: American Physiological Society, 2003.
سنة النشر: 2003
مصطلحات موضوعية: Genetically modified mouse, DNA, Complementary, Physiology, Mice, Transgenic, In Vitro Techniques, Biology, medicine.disease_cause, Binding, Competitive, digestive system, Mass Spectrometry, Mice, Physiology (medical), Gastrins, Escherichia coli, medicine, Animals, RNA, Messenger, Amino Acids, Intestinal Mucosa, Protein Precursors, Cells, Cultured, Chromatography, High Pressure Liquid, Fluorescent Dyes, Gastrin, Binding Sites, Microscopy, Confocal, Hepatology, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Gastroenterology, Epithelial Cells, Receptor, Cholecystokinin B, Recombinant Proteins, Stimulation, Chemical, In vitro, Epithelium, Small intestine, Cell biology, Kinetics, medicine.anatomical_structure, Biochemistry, Cell culture, Receptors, Cholecystokinin, Carcinogenesis
الوصف: Proliferation and carcinogenesis of the large intestinal epithelial cells (IEC) cells is significantly increased in transgenic mice that overexpress the precursor progastrin (PG) peptide. It is not known if the in vivo growth effects of PG on IEC cells are mediated directly or indirectly. Full-length recombinant human PG (rhPG1–80) was generated to examine possible direct effects of PG on IEC cells. Surprisingly, rhPG (0.1–1.0 nM) was more effective than the completely processed gastrin 17 (G17) peptide as a growth factor. Even though IEC cells did not express CCK1and CCK2receptors (-R), fluorescently labeled G17 and Gly-extended G17 (G-Gly) were specifically bound to the cells, suggesting the presence of binding proteins other than CCK1-R and CCK2-R on IEC cells. High-affinity ( Kd= 0.5–1.0 nM) binding sites for125I-rhPG were discovered on IEC cells that demonstrated relative binding affinity for gastrin-like peptides in the order PG ≥ COOH-terminally extended G17 ≥ G-Gly > G17 > *CCK-8 (* significant difference; P< 0.05). In conclusion, our studies demonstrate for the first time direct growth effects of the full-length precursor peptide on IEC cells in vitro that are apparently mediated by the high-affinity PG binding sites that were discovered on these cells.
تدمد: 1522-1547
0193-1857
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::34cbe5aa2ddd9915a8db0d25fb51395e
https://doi.org/10.1152/ajpgi.00351.2002
رقم الأكسشن: edsair.doi.dedup.....34cbe5aa2ddd9915a8db0d25fb51395e
قاعدة البيانات: OpenAIRE