Linked Life Data

10651866

Source:http://linkedlifedata.com/resource/pubmed/id/10651866

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-3-16
pubmed:abstractText
CXCR4 is the Gi protein-linked seven-transmembrane receptor for the alpha chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this alpha chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-25
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10651866-Animals, pubmed-meshheading:10651866-Astrocytes, pubmed-meshheading:10651866-Cells, Cultured, pubmed-meshheading:10651866-Cerebral Cortex, pubmed-meshheading:10651866-Chemokine CXCL12, pubmed-meshheading:10651866-Chemokines, CXC, pubmed-meshheading:10651866-Chemotaxis, pubmed-meshheading:10651866-Embryo, Mammalian, pubmed-meshheading:10651866-Growth Substances, pubmed-meshheading:10651866-HIV Envelope Protein gp120, pubmed-meshheading:10651866-Humans, pubmed-meshheading:10651866-Mitogen-Activated Protein Kinases, pubmed-meshheading:10651866-Neurons, pubmed-meshheading:10651866-PC12 Cells, pubmed-meshheading:10651866-Rats, pubmed-meshheading:10651866-Rats, Sprague-Dawley, pubmed-meshheading:10651866-Receptors, CXCR4, pubmed-meshheading:10651866-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10651866-Signal Transduction, pubmed-meshheading:10651866-Stem Cells, pubmed-meshheading:10651866-Transcription, Genetic
pubmed:year
2000
pubmed:articleTitle
Differential signalling of the chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
pubmed:affiliation
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 75724, Cedex 15, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't