Linked Life Data

14644469

Source:http://linkedlifedata.com/resource/pubmed/id/14644469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-3
pubmed:abstractText
Human immunodeficiency virus type-1 (HIV-1) infection is commonly associated with neuronal loss, as well as, cognitive and motor deficits collectively termed HIV-1-associated dementia (HAD). Function of the HIV-1 transcription factor Tat, activation of N-methyl-D-aspartate (NMDA)-type glutamate receptors, and subsequent rapid rises in free intracellular Ca2+ have been implicated in the development of this neurological disorder. However, the role of specific NMDA receptor modulatory sites in mediating effects of Tat has not been examined. The present studies examined the ability of two variants of Tat protein (1-100 nM), Tat 1-72 and Tat 1-86, to produce rapid rises in intracellular Ca2+ in organotypic slice cultures of rat hippocampus. Further, these studies evaluated the role of an NMDA receptor polyamine-sensitive site in mediating Tat-induced elevations in intracellular Ca2+. Brief exposure (10 min) to each variant of Tat protein (>1 nM) markedly increased levels of intracellular Ca2+ in each region of the hippocampus to as much as 145% of controls. In contrast, exposure of cultures to a deletion mutant of Tat protein devoid of amino acids 31-61 (Tat Delta31-61) did not produce changes in intracellular Ca2+ levels. Most significantly, exposure to the NMDA receptor antagonist dizocilpine (MK801 20 microM) and the polyamine site antagonist arcaine (10 microM) significantly attenuated increases in intracellular Ca2+ levels when co-administered with either the Tat 1-72 or Tat 1-86 amino acid variant of Tat. Thus, exposure of the hippocampus to Tat produces increases in intracellular Ca2+ levels that require function of an NMDA receptor polyamine-sensitive site and this may well contribute to the neurotoxic effects of HIV-1 infection. Polyamine-sensitive portions of this receptor may then represent novel therapeutic targets in the pharmacologic treatment of HAD-related neurotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
995
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-45
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14644469-AIDS Dementia Complex, pubmed-meshheading:14644469-Animals, pubmed-meshheading:14644469-Biguanides, pubmed-meshheading:14644469-Brain, pubmed-meshheading:14644469-Calcium, pubmed-meshheading:14644469-Excitatory Amino Acid Antagonists, pubmed-meshheading:14644469-Female, pubmed-meshheading:14644469-Gene Products, tat, pubmed-meshheading:14644469-HIV-1, pubmed-meshheading:14644469-Hippocampus, pubmed-meshheading:14644469-Male, pubmed-meshheading:14644469-Mutation, pubmed-meshheading:14644469-Nerve Degeneration, pubmed-meshheading:14644469-Neurons, pubmed-meshheading:14644469-Peptide Fragments, pubmed-meshheading:14644469-Polyamines, pubmed-meshheading:14644469-Rats, pubmed-meshheading:14644469-Rats, Sprague-Dawley, pubmed-meshheading:14644469-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:14644469-Up-Regulation, pubmed-meshheading:14644469-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2004
pubmed:articleTitle
The human immunodeficiency virus type-1 transcription factor Tat produces elevations in intracellular Ca2+ that require function of an N-methyl-D-aspartate receptor polyamine-sensitive site.
pubmed:affiliation
Department of Psychology, University of Kentucky, 115 Kastle Hall, Lexington, KY 40506-0044, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't