Linked Life Data

16623639

Source:http://linkedlifedata.com/resource/pubmed/id/16623639

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-4-20
pubmed:abstractText
HIV-associated dementia results from neuronal loss and an alteration of neuronal function due to a loss of synapses. While HIV infection in astrocytes is limited, astrocytes exhibit a chronic nonproductive infection that can lead to the release of neurotoxic proteins. Additionally, infection can disrupt the normal neurotrophic role of astrocytes that results in neuronal death. Gonadal steroid hormones are known to act as trophic and protective factors in the brain under a variety of normal and pathological conditions. In the present study, to determine if estrogen plays a role in the ability of Tat to function as a transcriptional activator within astrocytes, we examined the effect of estrogen on regulation of viral transcription. We utilized an immortalized human astrocyte cell line (SVGA) stably transfected with a reporter plasmid containing the HIV-1IIIB LTR driving the chloramphenicol acetyltransferase (CAT) gene. The amount of transcriptional activity was measured by quantifying the amount of CAT produced. We determined that 17beta-estradiol treatment (1 nM) had no effect on basal LTR activity. Following transfection with a Tat-expressing plasmid, there was a 100-fold increase in CAT production. This induction was reduced by 40% in cells pretreated with 17beta-estradiol. 17beta- Estradiol only suppressed transcription stimulated by Tat. Furthermore, we determined that this effect was specific to 17beta-estradiol and estrogen receptor agonists. This activity was limited to astrocytes as no effect was observed in a monocytic cell line. Finally, the mechanism of action did not involve an alteration in levels of Cdk9 or Cyclin T1 proteins necessary for Tat activation of the HIV-1 LTR. This study demonstrates a novel activity of 17beta-estradiol in glial cells that could play a role in the maintenance of neuronal health during HIV infection of the central nervous system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0889-2229
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16623639-Analysis of Variance, pubmed-meshheading:16623639-Astrocytes, pubmed-meshheading:16623639-Blotting, Western, pubmed-meshheading:16623639-Cell Line, Transformed, pubmed-meshheading:16623639-Cell Transformation, Viral, pubmed-meshheading:16623639-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:16623639-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16623639-Estradiol, pubmed-meshheading:16623639-Fluorescent Antibody Technique, pubmed-meshheading:16623639-Fluorescent Dyes, pubmed-meshheading:16623639-Gene Expression Regulation, Viral, pubmed-meshheading:16623639-Genes, Reporter, pubmed-meshheading:16623639-HIV-1, pubmed-meshheading:16623639-HeLa Cells, pubmed-meshheading:16623639-Humans, pubmed-meshheading:16623639-Plasmids, pubmed-meshheading:16623639-Promoter Regions, Genetic, pubmed-meshheading:16623639-Terminal Repeat Sequences, pubmed-meshheading:16623639-Transcription, Genetic, pubmed-meshheading:16623639-Transfection
pubmed:year
2006
pubmed:articleTitle
Estradiol negatively regulates HIV-LTR promoter activity in glial cells.
pubmed:affiliation
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA. mewils2@uky.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural