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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1994-12-20
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pubmed:abstractText |
Reactive oxygen species are thought to be messengers for nuclear factor (NF)-kappa B activation because its activation can be abrogated by antioxidants. However, this study identifies, for the first time, NF-kappa B activators that are insensitive to antioxidants. NF-kappa B activation that is induced by either calyculin A or okadaic acid (inhibitors of serine/threonine protein phosphatases 1 and 2A) is not blocked by N-acetylcysteine or dihydrolipoate in Jurkat and U937 cells. Nonetheless, these antioxidants block induction by TNF-alpha, lymphotoxin, and PMA. Unlike okadaic acid and calyculin A, neither TNF-alpha, lymphotoxin, nor PMA inhibited activities of phosphatases 1 and 2A. NF-kappa B activation induced by okadaic acid or calyculin A was not blocked by a myosin light chain kinase inhibitor, but was prevented by a protease inhibitor. The mitochondrial inhibitor, rotenone, also inhibited NF-kappa B activation by calyculin A; however, this inhibition was accompanied by a depletion of cellular ATP. These results suggest that 1) phosphatase inhibitors either target a component of signal transduction, which occurs downstream to an antioxidant-sensitive step or use distinct signaling pathways; 2) inhibition of phosphatases 1 and 2A is not a step in the pathway of TNF-alpha-, lymphotoxin-, or PMA-induced NF-kappa B activation; 3) myosin light chain kinase does not participate in NF-kappa B activation; and 4) activation of NF-kappa B by phosphatase inhibitors is controlled by proteases.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Ethers, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/calyculin A
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
153
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5008-15
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7963561-Antioxidants,
pubmed-meshheading:7963561-Base Sequence,
pubmed-meshheading:7963561-Cell Line,
pubmed-meshheading:7963561-Ethers, Cyclic,
pubmed-meshheading:7963561-Humans,
pubmed-meshheading:7963561-Molecular Sequence Data,
pubmed-meshheading:7963561-NF-kappa B,
pubmed-meshheading:7963561-Okadaic Acid,
pubmed-meshheading:7963561-Oxazoles,
pubmed-meshheading:7963561-Phosphoprotein Phosphatases,
pubmed-meshheading:7963561-Protein-Serine-Threonine Kinases,
pubmed-meshheading:7963561-RNA, Messenger,
pubmed-meshheading:7963561-Reactive Oxygen Species,
pubmed-meshheading:7963561-Signal Transduction
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pubmed:year |
1994
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pubmed:articleTitle |
Signal transduction for nuclear factor-kappa B activation. Proposed location of antioxidant-inhibitable step.
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pubmed:affiliation |
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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