pubmed-article:12167619 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0004112 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0132555 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C0961954 | lld:lifeskim |
pubmed-article:12167619 | lifeskim:mentions | umls-concept:C1100939 | lld:lifeskim |
pubmed-article:12167619 | pubmed:issue | 42 | lld:pubmed |
pubmed-article:12167619 | pubmed:dateCreated | 2002-10-15 | lld:pubmed |
pubmed-article:12167619 | pubmed:abstractText | Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-kappaB and C/EBPbeta, transcription factors responsible for the induction of iNOS. Activation of NF-kappaB as well as C/EBPbeta by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPbeta, and inhibition of RSV-tat-induced production of NO by deltap65, a dominant-negative mutant of p65, and deltaC/EBPbeta, a dominant-negative mutant of C/EBPbeta, suggest that RSV-tat induces iNOS through the activation of NF-kappaB and C/EBPbeta. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and deltaERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO through the inhibition of C/EBPbeta but not that of NF-kappaB. This study illustrates a novel role for HIV-1 tat in inducing the expression of iNOS in human astrocytes that may participate in the pathogenesis of HIV-associated dementia. | lld:pubmed |
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pubmed-article:12167619 | pubmed:language | eng | lld:pubmed |
pubmed-article:12167619 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12167619 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:12167619 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:12167619 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12167619 | pubmed:month | Oct | lld:pubmed |
pubmed-article:12167619 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:MaiKK | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:WoodCharlesC | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:JanaMalabendu... | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:DasguptaSubha... | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:LiuXiaojuanX | lld:pubmed |
pubmed-article:12167619 | pubmed:author | pubmed-author:PahanKalipada... | lld:pubmed |