Linked Life Data

12689815

Source:http://linkedlifedata.com/resource/pubmed/id/12689815

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-4-11
pubmed:abstractText
Ischemia/reperfusion of heart causes contractile dysfunction, necrosis and/or apoptosis and is a major cause of human death, but the molecular mechanisms are unclear. We show that ischemia alone (without reperfusion) is sufficient to induce apoptosis and mitochondrial dysfunction, and we have investigated the mechanism responsible; 30 and 60 min stop-flow ischemia in Langendorff-perfused rat hearts induced progressive (a). release of cytochrome c from mitochondria to cytosol, (b). inhibition of the mitochondrial respiratory functions, (c). activation of caspase-3-like protease activity and (d). DNA strand breaks (however, only 2% of myocyte nuclei were TUNEL positive at 60 min). Fifteen minutes pre-perfusion of hearts with cyclosporin A, an inhibitor of mitochondrial-permeability transition (MPT), largely prevented all these ischemic changes. Pre-perfusion of hearts with FK506, an inhibitor of calcineurin, caused no protection. Pre-perfusion with DEVD-CHO, an inhibitor of caspase-3-like proteases, completely prevented ischemia-induced DNA strand breaks, but only partially blocked cytochrome c release and mitochondrial respiratory inhibition. Reperfusion of hearts after 30 min ischemia further stimulated caspase activity and nuclear apoptosis. We conclude that ischemia-induced MPT causes release of cytochrome c, which then activates the caspases that execute apoptosis and feedback to cause further cytochrome c release. The MPT-induced cytochrome c release is also largely responsible for the ischemic respiratory inhibition, which might contribute to contractile dysfunction or necrosis at reperfusion.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
357-66
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia.
pubmed:affiliation
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. vb207@mole.bio.cam.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't