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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-14
pubmed:abstractText
Human neural stem cells (NSCs) grown in culture responded to extracellularly applied adenosine triphosphate (ATP), and the rate of proliferation increased as shown by immunocytochemical and RT-PCR analysis. Activation of P2 purinoceptors by ATP is coupled to the release of intracellular calcium ([Ca(2+)](i)) from thapsigargin-sensitive intracellular stores. ATP-induced proliferation was blocked by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase. Neither EGTA, a calcium chelator, nor caffeine had any effect on ATP-induced [Ca(2+)](i) increases. Multiblot kinase analysis, by which activation of 24 different kinases could be determined, showed that application of ATP to NSCs predominantly activated p70 ribosomal protein S6 kinase (p70 S6 kinase). As well, rapamycin, a p70 S6 kinase inhibitor, blocked the ATP-mediated proliferative response in NSCs. After outlining a role for p70 S6 kinase in ATP-mediated NSC proliferation, we examined the possibility that phosphatidylinositol 3-kinase (PI3-kinase) acts upstream of p70 S6 kinase. The application of wortmannin, a PI3-kinase inhibitor, decreased both ATP-mediated p70 S6 kinase activation and NSC proliferation. From these results, we conclude that ATP application to NSCs induces release of Ca(2+) from intracellular Ca(2+) stores and that this increase in intracellular Ca(2+) in turn promotes NSC proliferation. The increase in NSC proliferation observed following ATP application can also be mediated by PI3-kinase-dependent p70 S6 kinase activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
352-62
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12692902-Adenosine Triphosphate, pubmed-meshheading:12692902-Apoptosis, pubmed-meshheading:12692902-Blotting, Western, pubmed-meshheading:12692902-Calcium, pubmed-meshheading:12692902-Cell Division, pubmed-meshheading:12692902-Cell Survival, pubmed-meshheading:12692902-Cells, Cultured, pubmed-meshheading:12692902-Fetus, pubmed-meshheading:12692902-Humans, pubmed-meshheading:12692902-Immunohistochemistry, pubmed-meshheading:12692902-Neurons, pubmed-meshheading:12692902-Purinergic P2 Receptor Antagonists, pubmed-meshheading:12692902-Receptors, Purinergic P2, pubmed-meshheading:12692902-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12692902-Ribosomal Protein S6 Kinases, 70-kDa, pubmed-meshheading:12692902-Stem Cells, pubmed-meshheading:12692902-Telencephalon
pubmed:year
2003
pubmed:articleTitle
Adenosine triphosphate induces proliferation of human neural stem cells: Role of calcium and p70 ribosomal protein S6 kinase.
pubmed:affiliation
Brain Disease Research Center, Ajou University, Suwon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't