Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-2-14
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.
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
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
320 ( Pt 3)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
975-81
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1996
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.
pubmed:affiliation
Department of Biochemistry, Trinity College, Dublin 2, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't