Linked Life Data

12841647

Source:http://linkedlifedata.com/resource/pubmed/id/12841647

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-7-4
pubmed:abstractText
We have recently shown that the protective mechanism of ischemic preconditioning (PC) is impaired in the myocardium that survived infarction and underwent postinfarct ventricular remodeling. In this study, we examined the hypothesis that failure of PC to activate PKC-epsilon underlies the refractoriness of the remodeling heart to PC. Circumflex coronary arteries were ligated in rabbits to induce infarction and subsequent ventricular remodeling, and only sham operations were performed in controls. Hearts were isolated before (i.e. 4 days later) or after (i.e. 2 weeks later) remodeling of the left ventricle and used for isolated buffer-perfused heart experiments. Myocardial infarction was induced in isolated hearts by 30 min global ischemia/2 h reperfusion, and its size was measured by tetrazolium staining. Using separate groups of hearts, tissue biopsies were taken before and after PC, and PKC translocation was assessed by Western blotting. Areas infarcted in vivo by coronary ligation (CL) were excluded from subsequent infarct size/PKC analyses. In the hearts 4 days after CL, PC with 2 cycles of 5 min ischemia/5 min reperfusion induced PKC-epsilon translocation from cytosol to particulate fractions and limited infarct size to 40% of control value. In the hearts remodeled 2 weeks after CL, PC failed to induce PKC-epsilon translocation and infarct size limitation. In this group, PKC activity and hemodynamic responses to adenosine were similar to those in sham-operated controls. When remodeling after CL was prevented by valsartan infusion (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker, PC could induce both infarct limitation and PKC-epsilon translocation. The present results suggest that persistent activation of AT1 receptors during remodeling disturbed the PC signaling between G proteins and PKC-epsilon, which underlies the refractoriness of the remodeled myocardium to PC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0300-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
247
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12841647-Adenosine, pubmed-meshheading:12841647-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:12841647-Animals, pubmed-meshheading:12841647-Cytosol, pubmed-meshheading:12841647-GTP-Binding Proteins, pubmed-meshheading:12841647-Ischemic Preconditioning, Myocardial, pubmed-meshheading:12841647-Male, pubmed-meshheading:12841647-Myocardial Infarction, pubmed-meshheading:12841647-Myocardial Reperfusion, pubmed-meshheading:12841647-Protein Kinase C, pubmed-meshheading:12841647-Protein Kinase C-epsilon, pubmed-meshheading:12841647-Protein Transport, pubmed-meshheading:12841647-Rabbits, pubmed-meshheading:12841647-Receptors, Purinergic P1, pubmed-meshheading:12841647-Signal Transduction, pubmed-meshheading:12841647-Tetrazoles, pubmed-meshheading:12841647-Valine, pubmed-meshheading:12841647-Ventricular Remodeling
pubmed:year
2003
pubmed:articleTitle
Interruption of signal transduction between G protein and PKC-epsilon underlies the impaired myocardial response to ischemic preconditioning in postinfarct remodeled hearts.
pubmed:affiliation
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't