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ID 50676
FullText URL
Author
Akazawa, Y.
Kubo, M.
Zhang, R.
Matsumoto, K.
Yan, F.
Setiawan, H.
Takahashi, H.
Fujikura, Y.
Ogino, K.
Abstract
Nitric oxide (NO) is produced from the conversion of L-arginine by NO synthase (NOS) and regulates a variety of processes in the gastrointestinal tract. Considering the increased activity of arginase in colitis tissue, it is speculated that arginase could inhibit NO synthesis by competing for the same L-arginine substrate, resulting in the exacerbation of colitis. We examined the role of arginase and its relationship to NO metabolism in dextran sulfate sodium (DSS)-induced colitis. Experimental colitis was induced in mice by administration of 2.5% DSS in drinking water for 8 days. Treatment for arginase inhibition was done by once daily intraperitoneal injection of N-omega-hydroxy-norarginine (nor-NOHA). On day 8, we evaluated clinical parameters (body weight, disease activity index, and colon length), histological features, the activity and expression of arginase, L-arginine content, the expression of NO synthase (NOS), and the concentration of NO end-product (NOx: nitrite + nitrate). Administration of nor-NOHA improved the worsened clinical parameters and histological features in DSS-induced colitis. Treatment with nor-NOHA attenuated the increased activity of arginase, upregulation of arginase. at both mRNA and protein levels, and decreased the content of L-arginine in colonic tissue in the DSS-treated mice. Conversely, despite the decreased expression of NOS2 mRNA, the decreased concentration of NOx in colonic tissues was restored to almost normal levels. The consumption of L-arginine by arginase could lead to decreased production of NO from NOS, contributing to the pathogenesis of the colonic inflammation; thus, arginase inhibition might be effective for improving colitis.
Keywords
nitric oxide
N-omega-hydroxy-nor-L-arginine
L-arginine
NOx
dextran sulfate sodium
Published Date
2013-05
Publication Title
Free Radical Research
Volume
volume47
Issue
issue3
Publisher
Informa Healthcare
Start Page
137
End Page
145
ISSN
1071-5762
Content Type
Journal Article
Official Url
http://dx.doi.org/10.3109/10715762.2012.756980
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/50675
language
英語
File Version
author
Refereed
True
DOI
Web of Sience KeyUT