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dc.contributor.authorO'NEILL, LUKE ANTHONY JOHN
dc.date.accessioned2009-10-05T15:04:06Z
dc.date.available2009-10-05T15:04:06Z
dc.date.issued1997
dc.date.submitted1997en
dc.identifier.citationBrennan P, O'Neill LA. `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)? in Biochemical Journal, 320, (3), 1997, pp 975 - 981en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/33734
dc.descriptionPUBLISHEDen
dc.description.abstractThe 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.en
dc.format.extent488870 bytes
dc.format.extent975en
dc.format.extent981en
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherPortland Pressen
dc.relation.ispartofseriesBiochemical Journalen
dc.relation.ispartofseries320en
dc.relation.ispartofseries3en
dc.rightsYen
dc.subjectBiochemistryen
dc.title2-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)en
dc.typeJournal Articleen
dc.contributor.sponsorHealth Research Board
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneill


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