Linked Life Data

17828768

Source:http://linkedlifedata.com/resource/pubmed/id/17828768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-15
pubmed:abstractText
Early intracellular events responsible for cell-cycle induction by beta-amyloid (A beta) in neurons have not been identified yet. Extracellular signal-regulated kinases 1/2 (ERK1/2) have been identified in this pathway, and inhibition of ERK activity prevents cell-cycle activation and reduces neuronal death induced by A beta. To identify upstream events responsible for ERK activation, attention has been focused on integrins. Treatment of SH-SY5Y cells, differentiated by long-term exposure to 10 microM retinoic acid with a neutralizing anti-alpha1-integrin antibody significantly reduced A beta-induced neuronal death. However, cell-cycle analysis showed that treatment with anti-alpha1-integrin per se produced changes in the distribution of cell populations, thus hampering any effect on A beta-induced cell-cycle activation. 4-Amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-D)pyramide, an inhibitor of src protein kinases that colocalizes with focal adhesion kinase (FAK) and is involved in integrin signaling, was effective in reducing activation of the cell cycle and preventing induction of neuronal death by A beta while inhibiting ERK1/2 phosphorylation. Similar results were obtained when FAK expression was down-regulated by siRNA silencing. The present study identifies a sequence of early events in the toxic effect of A beta in neuronal cultures that involves interaction with integrins, activation of FAK/src, enhanced phosphorylation of ERK1/2, and induction of the cell cycle, all leading to neuronal death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1097-4547
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-5
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Integrins mediate beta-amyloid-induced cell-cycle activation and neuronal death.
pubmed:affiliation
Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't