|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
51
|
|
pubmed:dateCreated |
2004-12-13
|
|
pubmed:abstractText |
Transglutaminase 2 (TGase 2) expression is increased in inflammatory diseases. We demonstrated previously that inhibitors of TGase 2 reduce nitric oxide (NO) generation in a lipopolysaccharide (LPS)-treated microglial cell line. However, the precise mechanism by which TGase 2 promotes inflammation remains unclear. We found that TGase 2 activates the transcriptional activator nuclear factor (NF)-kappaB and thereby enhances LPS-induced expression of inducible nitric-oxide synthase. TGase 2 activates NF-kappaB via a novel pathway. Rather than stimulating phosphorylation and degradation of the inhibitory subunit alpha of NF-kappaB (I-kappaBalpha), TGase2 induces its polymerization. This polymerization results in dissociation of NF-kappaB and its translocation to the nucleus, where it is capable of up-regulating a host of inflammatory genes, including inducible nitric-oxide synthase and tumor necrosis factor alpha (TNF-alpha). Indeed, TGase inhibitors prevent depletion of monomeric I-kappaBalpha in the cytosol of cells overexpressing TGase 2. In an LPS-induced rat brain injury model, TGase inhibitors significantly reduced TNF-alpha synthesis. The findings are consistent with a model in which LPS-induced NF-kappaB activation is the result of phosphorylation of I-kappaBalpha by I-kappaB kinase as well as I-kappaBalpha polymerization by TGase 2. Safe and stable TGase2 inhibitors may be effective agents in diseases associated with inflammation.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
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/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
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, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Polymers,
http://linkedlifedata.com/resource/pubmed/chemical/Transglutaminases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/transglutaminase 2
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
17
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
53725-35
|
|
pubmed:dateRevised |
2011-10-27
|
|
pubmed:meshHeading |
pubmed-meshheading:15471861-Animals,
pubmed-meshheading:15471861-Blotting, Western,
pubmed-meshheading:15471861-Brain,
pubmed-meshheading:15471861-Cell Line, Tumor,
pubmed-meshheading:15471861-Cytosol,
pubmed-meshheading:15471861-DNA, Complementary,
pubmed-meshheading:15471861-Enzyme Inhibitors,
pubmed-meshheading:15471861-GTP-Binding Proteins,
pubmed-meshheading:15471861-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15471861-Genes, Reporter,
pubmed-meshheading:15471861-Humans,
pubmed-meshheading:15471861-I-kappa B Proteins,
pubmed-meshheading:15471861-Immunohistochemistry,
pubmed-meshheading:15471861-Inflammation,
pubmed-meshheading:15471861-Lipopolysaccharides,
pubmed-meshheading:15471861-Male,
pubmed-meshheading:15471861-Microglia,
pubmed-meshheading:15471861-Models, Biological,
pubmed-meshheading:15471861-NF-kappa B,
pubmed-meshheading:15471861-Nitric Oxide,
pubmed-meshheading:15471861-Nitric Oxide Synthase,
pubmed-meshheading:15471861-Nitric Oxide Synthase Type II,
pubmed-meshheading:15471861-Nitrites,
pubmed-meshheading:15471861-Phosphorylation,
pubmed-meshheading:15471861-Polymers,
pubmed-meshheading:15471861-Protein Binding,
pubmed-meshheading:15471861-Rats,
pubmed-meshheading:15471861-Rats, Sprague-Dawley,
pubmed-meshheading:15471861-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15471861-Temperature,
pubmed-meshheading:15471861-Time Factors,
pubmed-meshheading:15471861-Transfection,
pubmed-meshheading:15471861-Transglutaminases,
pubmed-meshheading:15471861-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15471861-Ubiquitin,
pubmed-meshheading:15471861-Up-Regulation
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Transglutaminase 2 induces nuclear factor-kappaB activation via a novel pathway in BV-2 microglia.
|
|
pubmed:affiliation |
Department of Neurology and Neuroscience, Weill Medical College of Cornell University and Burke Medical Research Institute, White Plains, NY 10605, USA.
|
|
pubmed:publicationType |
Journal Article
|
