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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2000-10-5
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pubmed:abstractText |
Crohn's disease is a chronic disease characterized by oxidant-induced tissue injury and increased intestinal permeability. A consequence of oxidative damage is the accumulation of DNA strand breaks and activation of poly(ADP-ribose) polymerase (PARP), which subsequently catalyzes ADP-ribosylation of target proteins. In this study, we assessed the role of PARP in the colitis seen in interleukin (IL)-10 gene-deficient mice. IL-10 gene-deficient mice demonstrated significant alterations in colonic cellular energy status in conjunction with increased permeability, proinflammatory cytokine release, and nitrosative stress. After 14 days of treatment with the PARP inhibitor 3-aminobenzamide, IL-10 gene-deficient mice demonstrated normalized colonic permeability; reduced tumor necrosis factor-alpha and interferon-gamma secretion, inducible nitric oxide synthase expression, and nitrotyrosine levels; and significantly attenuated inflammation. Time course studies demonstrated that 3-aminobenzamide rapidly altered cellular metabolic activity and decreased cellular lactate levels. This was associated with normalization of colonic permeability and followed by a downregulation of proinflammatory cytokine release. Our data demonstrate that inhibition of PARP activity results in a marked improvement of colonic inflammatory disease and a normalization of cellular metabolic function and intestinal permeability.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-aminobenzamide,
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Parp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G641-51
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10960365-Animals,
pubmed-meshheading:10960365-Benzamides,
pubmed-meshheading:10960365-Chronic Disease,
pubmed-meshheading:10960365-Colitis,
pubmed-meshheading:10960365-Disease Models, Animal,
pubmed-meshheading:10960365-Energy Metabolism,
pubmed-meshheading:10960365-Enzyme Inhibitors,
pubmed-meshheading:10960365-Inflammatory Bowel Diseases,
pubmed-meshheading:10960365-Interferon-gamma,
pubmed-meshheading:10960365-Interleukin-10,
pubmed-meshheading:10960365-Intestinal Absorption,
pubmed-meshheading:10960365-Intestinal Mucosa,
pubmed-meshheading:10960365-Mice,
pubmed-meshheading:10960365-Mice, Inbred Strains,
pubmed-meshheading:10960365-Mice, Knockout,
pubmed-meshheading:10960365-Neutrophils,
pubmed-meshheading:10960365-Nitric Oxide Synthase,
pubmed-meshheading:10960365-Nitric Oxide Synthase Type II,
pubmed-meshheading:10960365-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:10960365-Proteins,
pubmed-meshheading:10960365-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10960365-Tyrosine
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pubmed:year |
2000
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pubmed:articleTitle |
Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis.
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pubmed:affiliation |
University of Calgary, University of Alberta, Edmonton, Alberta T6G 2C2, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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