Linked Life Data

18691453

Source:http://linkedlifedata.com/resource/pubmed/id/18691453

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-2-20
pubmed:abstractText
Given that mutant huntingtin may cause dysregulation of gene expression in striatal neurons leading to the neuronal death, we examined the expression level of Bcl-2 interacting mediator of cell death (Bim) in immortalized wild type STHdh(Q7) and knock-in mutant STHdh(Q111) striatal cell lines to understand the underlying mechanism by which mutant huntingtin causes selective death of striatal neurons. Mutant STHdh(Q111) exhibited significantly increased expression level of Bim compared to STHdh(Q7). Serum deprivation resulted in potentiated apoptotic death in STHdh(Q111) compared to STHdh(Q7). However, the expression level of Bim was not changed with serum deprivation in both cell lines. Activation of pro-survival pathway with IGF-1 significantly attenuated serum deprivation-induced neuronal death in both cell lines and attenuated mutant huntingtin-mediated potentiated apoptotic death in STHdh(Q111). The level of active Akt was significantly elevated in STHdh(Q111) compared to STHdh(Q7) resulting in the phosphorylation of a FKHRL1, a forkhead transcription factor regulating Bim expression in neuronal cells. These data suggest that the presence of mutant huntingtin causes transcriptional dysregulation favoring apoptosis and that Akt pro-survival pathway in STHdh(Q111) is not compromised due to the presence of mutant huntingtin. Therefore, activation of this pathway may contribute to the protection of striatal neurons in Huntington's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0161-6412
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Increased expression of Bim contributes to the potentiation of serum deprivation-induced apoptotic cell death in Huntington's disease knock-in striatal cell line.
pubmed:affiliation
Department of Pharmacology, College of Medicine, Kangwon National University, Chunchon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't