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rdf:type |
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lifeskim:mentions |
umls-concept:C0009968,
umls-concept:C0027882,
umls-concept:C0038838,
umls-concept:C0043481,
umls-concept:C0332206,
umls-concept:C0475224,
umls-concept:C0521451,
umls-concept:C1159825,
umls-concept:C1514559,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1883709,
umls-concept:C2350483
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pubmed:issue |
1
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pubmed:dateCreated |
2001-12-28
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pubmed:abstractText |
Mitochondria are known to be involved in the early stage of apoptosis by releasing cytochrome c, caspase-9, and the second mitochondria-derived activator of caspases (Smac). We have reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduced superoxide production and ameliorated neuronal injury in the hippocampal CA1 subregion after global ischemia. However, the role of oxygen free radicals produced after ischemia/reperfusion in the mitochondrial signaling pathway has not been clarified. Five minutes of global ischemia was induced in male SOD1-transgenic (Tg) and wild-type (Wt) littermate rats. Cytosolic expression of cytochrome c and Smac and activation of caspases were evaluated by immunohistochemistry, Western blot, and caspase activity assay. Apoptotic cell death was characterized by DNA nick end and single-stranded DNA labeling. In the Wt animals, early superoxide production, mitochondrial release of cytochrome c, Smac, and cleaved caspase-9 were observed after ischemia. Active caspase-3 was subsequently increased, and 85% of the hippocampal CA1 neurons showed apoptotic DNA damage 3 d after ischemia. Tg animals showed less superoxide production and cytochrome c and Smac release. Subsequent active caspase-3 expression was not evident, and only 45% of the neurons showed apoptotic DNA damage. A caspase-3 inhibitor (N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone) reduced cell death only in Wt animals. These results suggest that overexpression of SOD1 reduced oxidative stress, thereby attenuating the mitochondrial release of cytochrome c and Smac, resulting in less caspase activation and apoptotic cell death. Oxygen free radicals may play a pivotal role in the mitochondrial signaling pathway of apoptotic cell death in hippocampal CA1 neurons after global ischemia.
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pubmed:grant |
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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/Carrier Proteins,
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/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
209-17
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11756504-Animals,
pubmed-meshheading:11756504-Animals, Genetically Modified,
pubmed-meshheading:11756504-Apoptosis,
pubmed-meshheading:11756504-Brain Ischemia,
pubmed-meshheading:11756504-Carrier Proteins,
pubmed-meshheading:11756504-Caspase 3,
pubmed-meshheading:11756504-Caspase 9,
pubmed-meshheading:11756504-Caspases,
pubmed-meshheading:11756504-Cytochrome c Group,
pubmed-meshheading:11756504-Cytoprotection,
pubmed-meshheading:11756504-DNA Damage,
pubmed-meshheading:11756504-Enzyme Inhibitors,
pubmed-meshheading:11756504-Gene Expression,
pubmed-meshheading:11756504-Hippocampus,
pubmed-meshheading:11756504-Immunohistochemistry,
pubmed-meshheading:11756504-Male,
pubmed-meshheading:11756504-Mitochondria,
pubmed-meshheading:11756504-Mitochondrial Proteins,
pubmed-meshheading:11756504-Neurons,
pubmed-meshheading:11756504-Rats,
pubmed-meshheading:11756504-Rats, Sprague-Dawley,
pubmed-meshheading:11756504-Signal Transduction,
pubmed-meshheading:11756504-Superoxide Dismutase,
pubmed-meshheading:11756504-Superoxides
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pubmed:year |
2002
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pubmed:articleTitle |
Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation.
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pubmed:affiliation |
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305-5487, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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