Linked Life Data

12059037

Source:http://linkedlifedata.com/resource/pubmed/id/12059037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-6-12
pubmed:abstractText
Mutations in the amyloid precursor protein (APP) gene are known as causative factors in the pathogenesis of early-onset familial Alzheimer's disease (FAD). In this study, the influence of the Swedish double-mutation form of APP (APPsw; KM670/671NL) on apoptosis regulation in PC12 cells was investigated. APPsw-transfected PC12 cells were compared with wild-type APP (APPwt)-expressing and vector-transfected PC12 cells with regard to their susceptibility to cell death induced by the reduction of trophic support or by additional treatment with staurosporine. Expression of APPsw markedly enhanced the level of apoptotic PC12 cells induced by serum reduction. A similar hypersensitivity of APPsw-expressing PC12 cells could be detected after differentiation with nerve growth factor under serum-reduced conditions. Likewise, the expression of APPsw rendered PC12 cells more vulnerable to staurosporine but only under serum-reduced conditions. This APPsw-effect disappeared in high serum-containing medium. Thus, expression of APPsw seems to enhance cellular sensitivity not in general but after the reduction of trophic factors probably by causing oxidative stress. This, in turn, may sensitize cells to secondary apoptotic stimuli. Moreover, the mutation-specific increase in vulnerability to cell death was only seen at the stage of apoptotic nuclei, but not using methods measuring cell death by determining metabolic activity or membrane integrity. Therefore, the expression of APPsw seems to affect specifically apoptotic cell death rather than overall cell death in vitro. Our study further emphasizes the pathogenic role of mutant APP and may provide new insights in the mechanisms underlying the massive neurodegeneration in brain from patients bearing the APPsw mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0895-8696
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-201
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12059037-Alzheimer Disease, pubmed-meshheading:12059037-Amyloid beta-Protein Precursor, pubmed-meshheading:12059037-Animals, pubmed-meshheading:12059037-Apoptosis, pubmed-meshheading:12059037-Culture Media, pubmed-meshheading:12059037-DNA Fragmentation, pubmed-meshheading:12059037-Enzyme Inhibitors, pubmed-meshheading:12059037-Flow Cytometry, pubmed-meshheading:12059037-Humans, pubmed-meshheading:12059037-In Situ Nick-End Labeling, pubmed-meshheading:12059037-L-Lactate Dehydrogenase, pubmed-meshheading:12059037-Mutation, pubmed-meshheading:12059037-Neurons, pubmed-meshheading:12059037-Oxidative Stress, pubmed-meshheading:12059037-PC12 Cells, pubmed-meshheading:12059037-Rats, pubmed-meshheading:12059037-Staurosporine, pubmed-meshheading:12059037-Tetrazolium Salts, pubmed-meshheading:12059037-Thiazoles
pubmed:year
2002
pubmed:articleTitle
Reduction of trophic support enhances apoptosis in PC12 cells expressing Alzheimer's APP mutation and sensitizes cells to staurosporine-induced cell death.
pubmed:affiliation
Department of Pharmacology, Biocenter, University of Frankfurt, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't