Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-3-16
pubmed:abstractText
Treatment of dopaminergic rat PC12 cells with human immunodeficiency virus, type 1 (HIV-1) Tat protein or tat cDNA inhibited the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for the dopamine biosynthetic pathway, as well as the production and release of dopamine into the culture medium. Moreover, the Tat addition to PC12 cells up-regulated the expression of the inducible cAMP early repressor (ICER), a specific member of the cAMP-responsive element modulator transcription factor family, in a cAMP-dependent manner. In turn, ICER overexpression abrogated the transcription activity of the TH promoter in PC12 cells, strongly suggesting ICER involvement in Tat-mediated inhibition of TH gene expression. In vivo injection of synthetic HIV-1 Tat protein into the striatum of healthy rats induced a subclinical Parkinson's-like disease that became manifested only when the animals were treated with amphetamine. As early as one week postinjection, the histochemical examination of the rat substantia nigra showed a reduced staining of neurons expressing TH followed by a loss of TH(+) neurons at later time points. As Tat protein can be locally released into the central nervous system by HIV-1-infected microglial cells, our findings may contribute to the explanation of the pathogenesis of the motorial abnormalities often reported in HIV-1 seropositive individuals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4159-65
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10660577-Animals, pubmed-meshheading:10660577-Behavior, Animal, pubmed-meshheading:10660577-Cyclic AMP, pubmed-meshheading:10660577-Cyclic AMP Response Element Modulator, pubmed-meshheading:10660577-DNA-Binding Proteins, pubmed-meshheading:10660577-Dopamine, pubmed-meshheading:10660577-Forskolin, pubmed-meshheading:10660577-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10660577-Gene Products, tat, pubmed-meshheading:10660577-HIV-1, pubmed-meshheading:10660577-Humans, pubmed-meshheading:10660577-Male, pubmed-meshheading:10660577-Mesencephalon, pubmed-meshheading:10660577-Microscopy, Electron, pubmed-meshheading:10660577-Oxidopamine, pubmed-meshheading:10660577-PC12 Cells, pubmed-meshheading:10660577-RNA, Messenger, pubmed-meshheading:10660577-Rats, pubmed-meshheading:10660577-Rats, Wistar, pubmed-meshheading:10660577-Repressor Proteins, pubmed-meshheading:10660577-Tyrosine 3-Monooxygenase, pubmed-meshheading:10660577-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2000
pubmed:articleTitle
HIV-1 Tat-mediated inhibition of the tyrosine hydroxylase gene expression in dopaminergic neuronal cells.
pubmed:affiliation
Department of Morphology and Embryology, Anatomy Section, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy. zlg@dns.unife.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't