Source:http://linkedlifedata.com/resource/pubmed/id/20381450
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6-7
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pubmed:dateCreated |
2010-6-21
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pubmed:abstractText |
We have previously reported that estradiol can protect heart mitochondria from the ischemia-induced mitochondrial permeability transition pore-related release of cytochrome c and subsequent apoptosis. In this study we investigated whether the effect of 17-beta-estradiol on ischemia-induced mitochondrial dysfunctions and apoptosis is mediated by activation of signaling protein kinases in a Langendorff-perfused rat heart model of stop-flow ischemia. We found that pre-perfusion of non-ischemic hearts with 100nM estradiol increased the resistance of subsequently isolated mitochondria to the calcium-induced opening of mitochondrial permeability transition pore and this was mediated by protein kinase G. Loading of the hearts with estradiol prevented ischemia-induced loss of cytochrome c from mitochondria and respiratory inhibition and these effects were reversed in the presence of the inhibitor of Akt kinase, NO synthase inhibitor L-NAME, guanylyl cyclase inhibitor ODQ and protein kinase G inhibitor KT5823. Estradiol prevented ischemia-induced activation of caspases and this was also reversed by KT5823. These findings suggest that estradiol may protect the heart against ischemia-induced injury activating the signaling cascade which involves Akt kinase, NO synthase, guanylyl cyclase and protein kinase G, and results in blockage of mitochondrial permeability transition pore-induced release of cytochrome c from mitochondria, respiratory inhibition and activation of caspases.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/KT 5823,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial permeability...
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pubmed:status |
MEDLINE
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Print
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pubmed:volume |
1797
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1012-7
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pubmed:meshHeading |
pubmed-meshheading:20381450-Animals,
pubmed-meshheading:20381450-Apoptosis,
pubmed-meshheading:20381450-Calcium,
pubmed-meshheading:20381450-Carbazoles,
pubmed-meshheading:20381450-Caspases,
pubmed-meshheading:20381450-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:20381450-Cytochromes c,
pubmed-meshheading:20381450-Enzyme Activation,
pubmed-meshheading:20381450-Estradiol,
pubmed-meshheading:20381450-Female,
pubmed-meshheading:20381450-Mitochondria, Heart,
pubmed-meshheading:20381450-Mitochondrial Membrane Transport Proteins,
pubmed-meshheading:20381450-Models, Cardiovascular,
pubmed-meshheading:20381450-Myocardial Reperfusion Injury,
pubmed-meshheading:20381450-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:20381450-Rats,
pubmed-meshheading:20381450-Rats, Wistar,
pubmed-meshheading:20381450-Signal Transduction
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pubmed:articleTitle |
Estradiol-induced protection against ischemia-induced heart mitochondrial damage and caspase activation is mediated by protein kinase G.
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pubmed:affiliation |
Institute for Biomedical Research, Department of Biochemistry, Kaunas University of Medicine, Eiveniu 4, LT-50009 Kaunas, Lithuania.
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pubmed:publicationType |
Journal Article,
In Vitro
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