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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
41
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
Synthesis of ADP-ribose polymers catalyzed by poly-(ADP-ribose) polymerase-1 (PARP-1) has been implicated in transcriptional regulation. Recent studies with PARP-1 null mice and PARP-1 inhibitors have also demonstrated that PARP-1 has an essential role in nuclear factor-kappaB (NF-kappaB)-dependent gene expression induced by various inflammatory stimuli. In this study, we used primary cultured mouse glial cells to investigate the role of poly(ADP-ribosyl)ation by PARP-1 in NF-kappaB-dependent gene expression. PARP-1 inhibitors and the antisense RNA for PARP-1 mRNA suppressed lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-alpha and inducible nitric-oxide synthase, suggesting that PARP-1 activity has a critical role in synthesis. Western blotting with anti-poly(ADP-ribose) antibody revealed that PARP-1 itself was mainly poly(ADP-ribosyl)ated in glial cells, i.e. automodified PARP-1 (AM-PARP). The amounts of AM-PARP were not affected by LPS treatment, but were decreased by PARP-1 inhibitors. Electrophoretic mobility shift assay revealed that PARP-1 inhibitors and the antisense RNA for PARP-1 mRNA reduced the LPS-induced DNA binding of NF-kappaB. Non-modified PARP-1 also reduced the DNA binding of NF-kappaB via its physical association with NF-kappaB, whereas AM-PARP had no effect. On the other hand, enhancement of the automodification of PARP-1 by the addition of NAD+, its substrate, promoted the DNA binding of NF-kappaB. Furthermore, in in vitro transcription assay, the addition of AM-PARP or NAD+ to nuclear extracts promoted NF-kappaB p50-dependent transcription. These results indicate that automodification of PARP-1 positively up-regulates formation of the NF-kappaB.DNA complex and enhances transcriptional activation. Therefore, AM-PARP may be critical for the NF-kappaB-dependent gene expression of some inflammatory mediators in glial cells.
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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/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Nfkb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42774-86
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15302869-Animals,
pubmed-meshheading:15302869-Blotting, Western,
pubmed-meshheading:15302869-Cell Nucleus,
pubmed-meshheading:15302869-Cell Survival,
pubmed-meshheading:15302869-Cells, Cultured,
pubmed-meshheading:15302869-Cytokines,
pubmed-meshheading:15302869-DNA,
pubmed-meshheading:15302869-Dose-Response Relationship, Drug,
pubmed-meshheading:15302869-Gene Expression Regulation,
pubmed-meshheading:15302869-Immunoprecipitation,
pubmed-meshheading:15302869-Inflammation,
pubmed-meshheading:15302869-Lipopolysaccharides,
pubmed-meshheading:15302869-Mice,
pubmed-meshheading:15302869-Mice, Inbred BALB C,
pubmed-meshheading:15302869-NF-kappa B,
pubmed-meshheading:15302869-NF-kappa B p50 Subunit,
pubmed-meshheading:15302869-Neuroglia,
pubmed-meshheading:15302869-Nitric Oxide Synthase,
pubmed-meshheading:15302869-Nitric Oxide Synthase Type II,
pubmed-meshheading:15302869-Nitrites,
pubmed-meshheading:15302869-Oligonucleotides, Antisense,
pubmed-meshheading:15302869-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:15302869-Protein Transport,
pubmed-meshheading:15302869-RNA, Antisense,
pubmed-meshheading:15302869-RNA, Messenger,
pubmed-meshheading:15302869-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15302869-Time Factors,
pubmed-meshheading:15302869-Transcription, Genetic,
pubmed-meshheading:15302869-Transcription Factors,
pubmed-meshheading:15302869-Transcriptional Activation,
pubmed-meshheading:15302869-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15302869-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Critical role of the automodification of poly(ADP-ribose) polymerase-1 in nuclear factor-kappaB-dependent gene expression in primary cultured mouse glial cells.
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pubmed:affiliation |
Pharmaceutical Research Center, Meiji Seika Kaisha Limited, 760 Moro-oka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
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pubmed:publicationType |
Journal Article
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