Linked Life Data

15314293

Source:http://linkedlifedata.com/resource/pubmed/id/15314293

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-8-17
pubmed:abstractText
Cell surface death receptor-mediated neuronal apoptosis, which is a critical component of neurodegeneration, is modulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Doxorubicin (Dox) induces neuronal death by the activation of death receptor pathways. Recently, we demonstrated that Dox-induced neuronal apoptosis is regulated by the balance of MMP-3 and TIMP-3 in rat cortical cultures. Inbred mouse strains exhibit differential susceptibility to cell death stimuli in vivo. Prior to employing transgenic approaches to further investigate the roles of TIMP-3 and MMP-3 in neuronal death, we examined whether inbred mice display strain-dependent vulnerability to Dox. We induced neuronal apoptosis with Dox in primary neuronal cultures established from cerebral cortices of embryonic day 15 C57BL/10 or C57BL/6 mice. Using fluorescence activated cell sorting for neurons, we found that C57BL/6 cortical cultures exhibit a 28% greater neuronal death following Dox treatment than C57BL/10. Real-time PCR of unstimulated cultures revealed that C57BL/10 cortical cultures have reduced basal mRNA levels encoding the pro-apoptotic proteins: Fas, FasL, and TIMP-3, but increased levels of the anti-apoptotic molecule MMP-3 as compared to C57BL/6. Furthermore, C57BL/10 cultures treated with Dox displayed an enhanced induction of mRNA transcripts that encode anti-apoptotic MMPs. These results show that C57BL/10 cortical cultures are more resistant to death receptor-mediated apoptotic cell death as compared to C57BL/6, and suggest that this difference is related to Fas, FasL, and MMP expression. Strain-dependent differences in response to apoptotic stimuli may be an important consideration for developing transgenic models of neurodegeneration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1360-8185
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
649-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Vulnerability of mouse cortical neurons to doxorubicin-induced apoptosis is strain-dependent and is correlated with mRNAs encoding Fas, Fas-Ligand, and metalloproteinases.
pubmed:affiliation
Departments of Neurosciences, University of New Mexico School of Medicine, Health Sciences Center, Albuquerque, NM 87131, USA. mwetzel@salud.unm.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.