Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6-7
pubmed:dateCreated
2010-6-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1797
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1012-7
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
pubmed:articleTitle
Estradiol-induced protection against ischemia-induced heart mitochondrial damage and caspase activation is mediated by protein kinase G.
pubmed:affiliation
Institute for Biomedical Research, Department of Biochemistry, Kaunas University of Medicine, Eiveniu 4, LT-50009 Kaunas, Lithuania.
pubmed:publicationType
Journal Article, In Vitro