Linked Life Data

18786092

Source:http://linkedlifedata.com/resource/pubmed/id/18786092

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-9-12
pubmed:abstractText
A plethora of apoptotic stimuli converge on the mitochondria and affect their membrane integrity, thereby eliciting release of multiple death-promoting factors residing in the mitochondrial intermembrane space into the cytosol. Among the death-promoting factors, a serine protease, high temperature requirement A2 (HtrA2) has drawn attention as a key player in the apoptosis pathways in different pathological conditions including myocardial ischemia/reperfusion injury. Heart ischemia/reperfusion results in HtrA2 translocation from the mitochondria to the cytosol, where it promotes cardiomyocyte apoptosis via a protease activity-dependent and caspase-mediated pathway. Once released, cytosolic HtrA2 causes X-chromosome-linked inhibitor of apoptosis protein (XIAP) degradation, caspase activation, and subsequent apoptosis. Consistent with the hypothesis, inhibition of HtrA2 improved postischemic myocardial contractile functions along with reduction of myocardial infarct size. The precise mechanism underlying HtrA2-induced apoptosis in mammalian cells has been studied through biochemical, structural, and genetic studies, in which HtrA2 promotes proteolytic activation of caspases through multiple pathways in heart ischemia. Therapeutic interventions that inhibit HtrA2 expression, translocation, or protease activity (such as by using the ucf-101 inhibitor) may provide an attractive therapeutics in the treatment of cardiovascular diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1755-5914
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-32
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Activation of HtrA2, a mitochondrial serine protease mediates apoptosis: current knowledge on HtrA2 mediated myocardial ischemia/reperfusion injury.
pubmed:affiliation
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't