Source:http://linkedlifedata.com/resource/pubmed/id/15188275
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2004-6-9
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pubmed:abstractText |
Mechanosensory hair cells of the inner ear are especially sensitive to death induced by exposure to aminoglycoside antibiotics. This aminoglycoside-induced hair cell death involves activation of an intrinsic program of cellular suicide. Aminoglycoside-induced hair cell death can be prevented by broad-spectrum inhibition of caspases, a family of proteases that mediate apoptotic and programmed cell death in a wide variety of systems. More specifically, aminoglycoside-induced hair cell death requires activation of caspase-9. Caspase-9 activation requires release of mitochondrial cytochrome c into the cytoplasm, indicating that aminoglycoside-induced hair cell death is mediated by the mitochondrial (or "intrinsic") cell death pathway. The Bcl-2 family of pro-apoptotic and anti-apoptotic proteins are important upstream regulators of the mitochondrial apoptotic pathway. Bcl-2 is an anti-apoptotic protein that localizes to the mitochondria and promotes cell survival by preventing cytochrome c release. Here we have utilized transgenic mice that overexpress Bcl-2 to examine the role of Bcl-2 in neomycin-induced hair cell death. Overexpression of Bcl-2 significantly increased hair cell survival following neomycin exposure in organotypic cultures of the adult mouse utricle. Furthermore, Bcl-2 overexpression prevented neomycin-induced activation of caspase-9 in hair cells. These results suggest that the expression level of Bcl-2 has important effects on the pathway(s) important for the regulation of aminoglycoside-induced hair cell death.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/DC-00461,
http://linkedlifedata.com/resource/pubmed/grant/DC-02854,
http://linkedlifedata.com/resource/pubmed/grant/DC-03576,
http://linkedlifedata.com/resource/pubmed/grant/DC-04661,
http://linkedlifedata.com/resource/pubmed/grant/DC-05082,
http://linkedlifedata.com/resource/pubmed/grant/F31 DC005082-01,
http://linkedlifedata.com/resource/pubmed/grant/F31 DC005082-02
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pubmed:keyword | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Neomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-3034
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2004 Wiley Periodicals, Inc. J Neurobiol 60: 89-100, 2004
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pubmed:issnType |
Print
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
89-100
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:15188275-Animals,
pubmed-meshheading:15188275-Anti-Bacterial Agents,
pubmed-meshheading:15188275-Apoptosis,
pubmed-meshheading:15188275-Caspase 9,
pubmed-meshheading:15188275-Caspases,
pubmed-meshheading:15188275-Cell Survival,
pubmed-meshheading:15188275-Enzyme Activation,
pubmed-meshheading:15188275-Hair Cells, Auditory, Inner,
pubmed-meshheading:15188275-Immunohistochemistry,
pubmed-meshheading:15188275-Mice,
pubmed-meshheading:15188275-Mice, Transgenic,
pubmed-meshheading:15188275-Microscopy, Confocal,
pubmed-meshheading:15188275-Neomycin,
pubmed-meshheading:15188275-Organ Culture Techniques,
pubmed-meshheading:15188275-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15188275-Saccule and Utricle
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pubmed:year |
2004
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pubmed:articleTitle |
Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro.
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pubmed:affiliation |
Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, 98195-7293, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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