PMID- 21305324
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20211020
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Linking)
VI  - 46
IP  - 5
DP  - 2011 May
TI  - Nitric oxide induces HIF-1alpha stabilization and expression of intestinal trefoil 
      factor in the damaged rat jejunum and modulates ulcer healing.
PG  - 565-76
LID - 10.1007/s00535-011-0374-1 [doi]
AB  - 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 (7.5 mg/kg, 
      s.c., twice), and a time course analysis of damage was performed (24-96 h after 
      the first administration). In these animals, the role of nitric oxide was 
      analyzed by using 1400W, a selective iNOS activity inhibitor (5 mg/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-1alpha and ITF. RESULTS: Indomethacin induced damage in the 
      jejunum that was apparent at 24 h and peaked at 48-72 h. An increase in iNOS, 
      HIF-1alpha, ITF and nitrated proteins was observed in the injured jejunum. 
      Immunoprecipitation of HIF-1alpha 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-1alpha stabilization and 
      HIF-1alpha 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-1alpha stabilization, probably through S-nitrosylation, and ITF expression in 
      goblet cells of the damaged jejunum of indomethacin-treated rats and mediates 
      ulcer healing.
FAU - Riano, A
AU  - Riano A
AD  - Department of Pharmacology and CIBERehd, Faculty of Medicine, University of 
      Valencia, Avda. Blasco Ibanez 15-17, 46010 Valencia, Spain.
FAU - Ortiz-Masia, D
AU  - Ortiz-Masia D
FAU - Velazquez, M
AU  - Velazquez M
FAU - Calatayud, S
AU  - Calatayud S
FAU - Esplugues, J V
AU  - Esplugues JV
FAU - Barrachina, Maria Dolores
AU  - Barrachina MD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110209
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Imines)
RN  - 0 (N-((3-(aminomethyl)phenyl)methyl)ethanimidamide)
RN  - 0 (Peptides)
RN  - 0 (Trefoil Factor-2)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/toxicity
MH  - Goblet Cells/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Imines/pharmacology
MH  - Immunoprecipitation
MH  - Indomethacin/*toxicity
MH  - Intestinal Mucosa/metabolism
MH  - Jejunum/drug effects/pathology
MH  - Male
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Peptic Ulcer/chemically induced/pathology
MH  - Peptides/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Trefoil Factor-2
EDAT- 2011/02/10 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/02/10 06:00
PHST- 2010/03/16 00:00 [received]
PHST- 2010/12/23 00:00 [accepted]
PHST- 2011/02/10 06:00 [entrez]
PHST- 2011/02/10 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - 10.1007/s00535-011-0374-1 [doi]
PST - ppublish
SO  - J Gastroenterol. 2011 May;46(5):565-76. doi: 10.1007/s00535-011-0374-1. Epub 2011 
      Feb 9.