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NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION
- Source :
- Arquivos de Gastroenterologia, Vol 51, Iss 4, Pp 302-308 (2014)
- Publication Year :
- 2014
- Publisher :
- Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia (IBEPEGE), 2014.
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Abstract
- Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.
Details
- Language :
- English
- ISSN :
- 16784219 and 00042803
- Volume :
- 51
- Issue :
- 4
- Database :
- Directory of Open Access Journals
- Journal :
- Arquivos de Gastroenterologia
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.07ad335021324309853c4b5fee51c32e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1590/S0004-28032014000400007