Linked Life Data

17522316

Source:http://linkedlifedata.com/resource/pubmed/id/17522316

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2007-5-24
pubmed:abstractText
A pathological hallmark of Alzheimer's disease is accumulation of amyloid-beta peptide (Abeta) in senile plaques. Abeta has also been implicated in vascular degeneration in cerebral amyloid angiopathy because of its cytotoxic effects on non-neuronal cells, including cerebral endothelial cells (CECs). We explore the role of apoptosis signal-regulating kinase 1 (ASK1) in Abeta-induced death in primary cultures of murine CECs. Abeta induced ASK1 dephosphorylation, which could be prevented by selective inhibition of protein phosphatase 2A (PP2A) but not PP2B. ASK1 dephosphorylation resulted in its dissociation from 14-3-3. ASK1, released from 14-3-3 inhibition, activated p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. p53, a proapoptotic transcription factor, in turn transactivated the expression of Bax, a proapoptotic protein. Transfection with various dominant-negative mutants (DNs), including ASK1 DN and p38MAPK DN, suppressed Abeta-induced p38MAPK activation, p53 phosphorylation, and Bax upregulation and partially prevented CEC death. Bax knockdown using a bax small interfering RNA strategy also reduced Bax expression and subsequent CEC death. These results suggest that Abeta activates the ASK1-p38MAPK-p53-Bax cascade to cause CEC death in a PP2A-dependent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5719-29
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Apoptosis signal-regulating kinase 1 in amyloid beta peptide-induced cerebral endothelial cell apoptosis.
pubmed:affiliation
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110, Taiwan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't