Inhibiting protein arginine deiminases has antioxidant consequences
Document Type
Article
Publication Date
4-1-2015
Abstract
Ulcerative colitis is a dynamic, idiopathic, chronic inflammatory condition that carries a high colon cancer risk. We previously showed that Cl-amidine, a small-molecule inhibitor of the protein arginine deiminases, suppresses colitis in mice. Because colitis is defined as inflammation of the colon associated with infiltration of white blood cells that release free radicals and citrullination is an inflammationdependent process, we asked whether Cl-amidine has antioxidant properties. Here we show that colitis induced with azoxymethane via intraperitoneal injection 1 2%dextran sulfate sodium in the drinking water is suppressed by Cl-amidine (also given in the drinking water). Inducible nitric oxide synthase, an inflammatory marker, was also downregulated in macrophages by Cl-amidine. Because epithelial cell DNA damage associated with colitis is at least in part a result of an oxidative burst from overactive leukocytes, we tested the hypothesis that Cl-amidine can inhibit leukocyte activation, as well as subsequent target epithelial cell DNA damage in vitro and in vivo. Results are consistent with this hypothesis, and because DNA damage is a procancerous mechanism, our data predict that Clamidine will not only suppress colitis, but we hypothesize that it may prevent colon cancer associated with colitis.
Publication Title
Journal of Pharmacology and Experimental Therapeutics
Volume
353
Issue
1
First Page
64
Last Page
70
Digital Object Identifier (DOI)
10.1124/jpet.115.222745
PubMed ID
25635139
ISSN
00223565
E-ISSN
15210103
Citation Information
Witalison, Cui, X., Hofseth, A. B., Subramanian, V., Causey, C. P., Thompson, P. R., & Hofseth, L. J. (2015). Inhibiting Protein Arginine Deiminases Has Antioxidant Consequences. The Journal of Pharmacology and Experimental Therapeutics, 353(1), 64–70. https://doi.org/10.1124/jpet.115.222745