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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Synapsins,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1044-7431
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
78-96
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11161471-Adenoviridae,
pubmed-meshheading:11161471-Animals,
pubmed-meshheading:11161471-Apoptosis,
pubmed-meshheading:11161471-Brain,
pubmed-meshheading:11161471-Caspase 3,
pubmed-meshheading:11161471-Caspase 9,
pubmed-meshheading:11161471-Caspases,
pubmed-meshheading:11161471-Cell Differentiation,
pubmed-meshheading:11161471-Cells, Cultured,
pubmed-meshheading:11161471-Cerebellum,
pubmed-meshheading:11161471-Coculture Techniques,
pubmed-meshheading:11161471-Cytomegalovirus,
pubmed-meshheading:11161471-Gene Expression,
pubmed-meshheading:11161471-Genetic Vectors,
pubmed-meshheading:11161471-Hippocampus,
pubmed-meshheading:11161471-Mitochondria,
pubmed-meshheading:11161471-Neuroglia,
pubmed-meshheading:11161471-Neurons,
pubmed-meshheading:11161471-Potassium,
pubmed-meshheading:11161471-Promoter Regions, Genetic,
pubmed-meshheading:11161471-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11161471-Rats,
pubmed-meshheading:11161471-Rats, Sprague-Dawley,
pubmed-meshheading:11161471-Synapsins,
pubmed-meshheading:11161471-Transgenes,
pubmed-meshheading:11161471-Tubulin,
pubmed-meshheading:11161471-bcl-X Protein
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pubmed:year |
2001
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pubmed:articleTitle |
Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors.
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pubmed:affiliation |
Neuro-Regeneration Laboratory, University of Tübingen, Medical School, Verfügungsgebaude, Auf der Morgenstelle 15, Tübingen, 72076, Germany. kuegler@uni-tuebingen.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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