Linked Life Data

20211186

Source:http://linkedlifedata.com/resource/pubmed/id/20211186

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-6-14
pubmed:abstractText
Calpains contribute to reperfusion-induced myocardial cell death. However, it remains controversial whether its activation occurs during ischemia or reperfusion. We investigated the regulation and time-course of calpain activation secondary to transient ischemia and the efficacy of its inhibition at reperfusion as a therapeutic strategy to limit infarct size. In isolated rat hearts (Sprague-Dawley), ischemia induced a time-dependent translocation of m-calpain to the membrane that was not associated with calpain activation as assessed by proteolysis of its substrate alpha-fodrin. Translocation of calpain was dependent on Ca(2+) entry through reverse mode Na(+)/Ca(2+)-exchange and was independent of acidosis. Calpain activation occurred during reperfusion, but only after intracellular pH (pHi) normalization, and was not prevented by inhibiting its translocation during ischemia with methyl-beta-cyclodextrin. The intravenous infusion of MDL-28170 in an in vivo rat model with transient coronary occlusion during the first minutes of reperfusion resulted in a reduction of infarct size (43.9+/-3.9% vs. 60.2+/-4.7, P=0.046, n=18) and alpha-fodrin degradation. These results suggest that (1) Ca(2+)-induced calpain translocation to the membrane during ischemia is independent of its activation, (2) intracellular acidosis inhibits calpain activation during ischemia and pHi normalization allows activation upon reperfusion, and (3) calpain inhibition at the time of reperfusion appears as a potentially useful strategy to limit infarct size.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1095-8584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Calpain translocation and activation as pharmacological targets during myocardial ischemia/reperfusion.
pubmed:affiliation
Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't