Document Detail


Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease.
MedLine Citation:
PMID:  19932165     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Here we examined the therapeutic effects of 9- or 10-nitro-octadecenoic oleic acid (OA-NO(2)) and native oleic acid (OA) in a mouse model of colitis. OA-NO(2) reduced the disease activity index and completely prevented dextran sulfate sodium-induced colon shortening and the increase in colonic p65 expression. Increased PPARgamma expression was observed in colon samples as well as in cells after OA-NO(2) administration, whereas no effect was seen with OA. This induction of PPARgamma expression was completely abolished by the PPARgamma antagonist GW9662. 5-Aminosalicylic acid, an anti-inflammatory drug routinely used in the management of inflammatory bowel disease, also increased PPARgamma expression but to a lesser extent. Altogether, these findings demonstrate that administration of OA-NO(2) attenuates colonic inflammation and improves clinical symptoms in experimental inflammatory bowel disease. This protection involves activation of colonic PPARgamma.
Authors:
Sara Borniquel; Emmelie A Jansson; Marsha P Cole; Bruce A Freeman; Jon O Lundberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-20
Journal Detail:
Title:  Free radical biology & medicine     Volume:  48     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-06-03     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-505     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Culture Techniques / methods
Fatty Acids / metabolism
Female
Free Radicals
Gene Expression Regulation, Enzymologic*
Inflammatory Bowel Diseases / genetics*,  metabolism*
Mesalamine / pharmacology
Mice
Mice, Inbred BALB C
Models, Biological
Nitric Oxide / metabolism
Oleic Acid / metabolism
PPAR gamma / metabolism*
Up-Regulation*
Grant Support
ID/Acronym/Agency:
R01 HL064937/HL/NHLBI NIH HHS; R01 HL064937-09/HL/NHLBI NIH HHS; R01 HL58115/HL/NHLBI NIH HHS; R01 HL64937/HL/NHLBI NIH HHS; R37 HL058115/HL/NHLBI NIH HHS; R37 HL058115-15/HL/NHLBI NIH HHS; T32DK007052-34/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Free Radicals; 0/PPAR gamma; 2UMI9U37CP/Oleic Acid; 31C4KY9ESH/Nitric Oxide; 4Q81I59GXC/Mesalamine
Comments/Corrections

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