Linked Life Data

11514300

Source:http://linkedlifedata.com/resource/pubmed/id/11514300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-8-21
pubmed:abstractText
Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed DeltaPsi(m), as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome c immunostaining. Activation of mitoK(ATP) channel with diazoxide (100 micromol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized DeltaPsi(m). This protection was blocked by 5-hydroxydecanoate (500 micromol/l), a mitoK(ATP) channel-selective inhibitor, but not by HMR-1098 (30 micromol/l), a putative sarcolemmal K(ATP) channel-selective inhibitor. Dissipation of DeltaPsi(m) also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts DeltaPsi(m) and induces apoptosis, which are prevented by the activation of the mitoK(ATP) channel. This further emphasizes the therapeutic significance of mitoK(ATP) channel agonists in the prevention of ischemia-reperfusion cell injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1295-303
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11514300-Animals, pubmed-meshheading:11514300-Animals, Newborn, pubmed-meshheading:11514300-Apoptosis, pubmed-meshheading:11514300-Benzamides, pubmed-meshheading:11514300-Cell Hypoxia, pubmed-meshheading:11514300-Cell Survival, pubmed-meshheading:11514300-Cells, Cultured, pubmed-meshheading:11514300-Cytochrome c Group, pubmed-meshheading:11514300-Cytoprotection, pubmed-meshheading:11514300-Decanoic Acids, pubmed-meshheading:11514300-Diazoxide, pubmed-meshheading:11514300-Hydroxy Acids, pubmed-meshheading:11514300-In Situ Nick-End Labeling, pubmed-meshheading:11514300-Membrane Potentials, pubmed-meshheading:11514300-Mitochondria, Heart, pubmed-meshheading:11514300-Myocardium, pubmed-meshheading:11514300-Potassium Channel Blockers, pubmed-meshheading:11514300-Potassium Channels, pubmed-meshheading:11514300-Rats, pubmed-meshheading:11514300-Vasodilator Agents
pubmed:year
2001
pubmed:articleTitle
Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.