{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:53:01Z","timestamp":1790909581441,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,12,15]]},"abstract":"<jats:p>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 \u03baB (NF\u03baB). In agreement with other studies, we have shown that PDTC inhibits NF\u03baB 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\u03baB on a sensitive thiol, possibly on the p50 subunit (which was detected in NF\u03baB 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\u03baB\u2013DNA binding in vitro. On the basis of these results we suggest that, while NF\u03baB 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.<\/jats:p>","DOI":"10.1042\/bj3200975","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:51:59Z","timestamp":1439243519000},"page":"975-981","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["2-mercaptoethanol restores the ability of nuclear factor \u03baB (NF \u03baB) 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\u03baB by PDTC"],"prefix":"10.1042","volume":"320","author":[{"given":"Paul","family":"BRENNAN","sequence":"first","affiliation":[{"name":"1Department of Biochemistry, Trinity College, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A. J.","family":"O'NEILL","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry, Trinity College, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/320\/3\/975\/622716\/bj3200975.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/320\/3\/975\/622716\/bj3200975.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:16:58Z","timestamp":1637713018000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/320\/3\/975\/32984\/2-mercaptoethanol-restores-the-ability-of-nuclear"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1996,12,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3200975","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12,15]]}}}