caa a22 4500 445888997 CHVBK 20180317145609.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00535-011-0374-1 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0374-1 Nitric oxide induces HIF-1α stabilization and expression of intestinal trefoil factor in the damaged rat jejunum and modulates ulcer healing [Elektronische Daten] [A. Riaño, D. Ortiz-Masià, M. Velázquez, S. Calatayud, J. Esplugues, Maria Barrachina] Background: The induction of intestinal trefoil factor (ITF) has been reported to depend on hypoxia-inducible factor-1 (HIF-1). Nitric oxide modulates HIF-1 activity. The present study aims to analyze the role of nitric oxide in jejunum damage induced by indomethacin and its ability to modulate epithelial function through the expression of ITF. Methods: Rats received indomethacin (7.5mg/kg, s.c., twice), and a time course analysis of damage was performed (24-96h after the first administration). In these animals, the role of nitric oxide was analyzed by using 1400W, a selective iNOS activity inhibitor (5mg/kg, i.p./day), on: (1) intestinal damage, (2) ulcer healing, (3) the presence of nitrated proteins in the jejunum and (4) the protein expression of inducible nitric oxide synthase (iNOS), HIF-1α and ITF. Results: Indomethacin induced damage in the jejunum that was apparent at 24h and peaked at 48-72h. An increase in iNOS, HIF-1α, ITF and nitrated proteins was observed in the injured jejunum. Immunoprecipitation of HIF-1α allowed determination of the nitration/nitrosylation of this protein by using nitrotyrosine and nitrocysteine antibodies. Blockade of iNOS activity did not significantly modify damage or iNOS expression, but did significantly impede ITF induction, HIF-1α stabilization and HIF-1α detection with antibodies against nitrated proteins. In parallel to these results, pre-treatment with 1400W delayed the healing of the ulcer provoked by indomethacin. Conclusions: These results suggest that iNOS-derived NO is involved in HIF-1α stabilization, probably through S-nitrosylation, and ITF expression in goblet cells of the damaged jejunum of indomethacin-treated rats and mediates ulcer healing. Springer, 2011 HIF-1 nationallicence ITF nationallicence Nitric oxide nationallicence Indomethacin nationallicence Intestinal damage nationallicence Nitrosylation nationallicence Riaño A. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Ortiz-Masià D. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Velázquez M. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Calatayud S. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Esplugues J. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Barrachina Maria Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 565-576 0944-1174 46:5<565 2011 46 535 https://doi.org/10.1007/s00535-011-0374-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0374-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Riaño A. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 700 1- Ortiz-Masià D. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 700 1- Velázquez M. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 700 1- Calatayud S. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 700 1- Esplugues J. Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 700 1- Barrachina Maria Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Avda. Blasco Ibanez, 15-17, 46010, Valencia, Spain aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 565-576 0944-1174 46:5<565 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer