rdf:type |
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0012854,
umls-concept:C0017817,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0021764,
umls-concept:C0025402,
umls-concept:C0030011,
umls-concept:C0079904,
umls-concept:C0084183,
umls-concept:C0085732,
umls-concept:C0332120,
umls-concept:C0441712,
umls-concept:C1145667,
umls-concept:C1439852,
umls-concept:C1518434
|
pubmed:dateCreated |
1997-2-14
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pubmed:abstractText |
The metal chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) has been used extensively in studies implicating reactive oxygen intermediates in the activation of nuclear factor kappa B (NF kappa B). In agreement with other studies, we have shown that PDTC inhibits NF kappa B activation in response to the pro-inflammatory cytokines interleukin 1 (IL1) and tumour necrosis factor (TNF). However, we have found that the inhibition was reversed by treatment of inhibited nuclear extracts with the reducing agent 2-mercaptoethanol. This was observed in extracts prepared from IL1-treated EL4.NOB-1 thymoma cells and TNF-treated Jurkat E6.1 lymphoma cells. These results suggested that the inhibition was caused by oxidation of NF kappa B on a sensitive thiol, possibly on the p50 subunit (which was detected in NF kappa B complexes in both cell types), and not by inhibition of the activation pathway. The possibility that PDTC was acting as a pro-oxidant was therefore investigated. PDTC caused an increase in oxidized glutathione, suggesting that it acts as an oxidizing agent in the cells tested rather than as an anti-oxidant. Similar results were obtained with diamide, a compound designed to oxidize glutathione. Finally, an increase in the ratio of oxidized to reduced glutathione was shown to inhibit NF kappa B-DNA binding in vitro. On the basis of these results we suggest that, while NF kappa B activation is unaffected by PDTC, DNA binding is inhibited through a mechanism involving a shift towards oxidizing conditions, and that this is the mechanism of action of both PDTC and diamide in the cells tested here.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-1314883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-1482376,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-1643256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-2065663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-4388022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7416462,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7499370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7536858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7539260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7592825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7718619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7841193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-7857277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8011280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8174544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8255759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8371761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8493089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8497253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8674662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-8674694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-9383399,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9003388-942051
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Diamide,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Mercaptoethanol,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/prolinedithiocarbamate
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0264-6021
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
320 ( Pt 3)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
975-81
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9003388-Animals,
pubmed-meshheading:9003388-Antioxidants,
pubmed-meshheading:9003388-DNA-Binding Proteins,
pubmed-meshheading:9003388-Diamide,
pubmed-meshheading:9003388-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:9003388-Glutathione,
pubmed-meshheading:9003388-Humans,
pubmed-meshheading:9003388-Interleukin-1,
pubmed-meshheading:9003388-Mercaptoethanol,
pubmed-meshheading:9003388-Mice,
pubmed-meshheading:9003388-NF-kappa B,
pubmed-meshheading:9003388-Nuclear Proteins,
pubmed-meshheading:9003388-Oxidation-Reduction,
pubmed-meshheading:9003388-Proline,
pubmed-meshheading:9003388-Protein Binding,
pubmed-meshheading:9003388-Thiocarbamates,
pubmed-meshheading:9003388-Thymoma,
pubmed-meshheading:9003388-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
2-mercaptoethanol restores the ability of nuclear factor kappa B (NF kappa B) to bind DNA in nuclear extracts from interleukin 1-treated cells incubated with pyrollidine dithiocarbamate (PDTC). Evidence for oxidation of glutathione in the mechanism of inhibition of NF kappa B by PDTC.
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pubmed:affiliation |
Department of Biochemistry, Trinity College, Dublin 2, Ireland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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