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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2000-7-11
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pubmed:abstractText |
A toxic dose of acetaminophen (APAP) reduces the activity of NF-kappaB in mouse liver. NF-kappaB inactivation may be important for APAP toxicity, as this transcription factor can play a central role in maintaining hepatic viability. We recently reported that APAP likewise inhibits serum growth factor activation of NF-kappaB in a mouse hepatoma cell line (Hepa 1-6 cells). Here we present evidence that APAP's antioxidant activity may be involved in this NF-kappaB inhibition in Hepa 1-6 cells. Like the antioxidants N-acetylcysteine (NAC) and pyrrolidinedithiocarbamate (PDTC), APAP was found to suppress the H(2)O(2)-induced oxidation of an intracellular reactive oxygen species probe (dihydrodichlorofluorescein) in Hepa 1-6 cells. Treatment of Hepa 1-6 cells with H(2)O(2) was sufficient for NF-kappaB activation and IkappaBalpha degradation, and APAP was able to block both of these events. The APAP inhibition of NF-kappaB activation by serum growth factors may also be due to APAP's antioxidant activity, as the antioxidants NAC and PDTC likewise inhibit this activation. The potential role of NF-kappaB and oxidant-based growth factor signal transduction in APAP toxicity is discussed.
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pubmed:grant |
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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/2,7-dihydrodichlorofluorescein...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetaminophen,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Non-Narcotic,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Probes,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluoresceins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/pyrrolidine dithiocarbamic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1096-6080
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
370-5
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pubmed:dateRevised |
2010-9-17
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pubmed:meshHeading |
pubmed-meshheading:10828269-Acetaminophen,
pubmed-meshheading:10828269-Acetylcysteine,
pubmed-meshheading:10828269-Analgesics, Non-Narcotic,
pubmed-meshheading:10828269-Animals,
pubmed-meshheading:10828269-Antioxidants,
pubmed-meshheading:10828269-Blotting, Western,
pubmed-meshheading:10828269-Carcinoma, Hepatocellular,
pubmed-meshheading:10828269-DNA Probes,
pubmed-meshheading:10828269-DNA-Binding Proteins,
pubmed-meshheading:10828269-Fluoresceins,
pubmed-meshheading:10828269-Hydrogen Peroxide,
pubmed-meshheading:10828269-I-kappa B Proteins,
pubmed-meshheading:10828269-Mice,
pubmed-meshheading:10828269-NF-kappa B,
pubmed-meshheading:10828269-Oxidation-Reduction,
pubmed-meshheading:10828269-Pyrrolidines,
pubmed-meshheading:10828269-Signal Transduction,
pubmed-meshheading:10828269-Thiocarbamates,
pubmed-meshheading:10828269-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Acetaminophen inhibits NF-kappaB activation by interfering with the oxidant signal in murine Hepa 1-6 cells.
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pubmed:affiliation |
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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