Linked Life Data

20337662

Source:http://linkedlifedata.com/resource/pubmed/id/20337662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-7-19
pubmed:abstractText
1. Preconditioning has been proposed to protect the myocardium by inhibiting glycogen-synthase kinase (GSK) 3beta. The aim of the present study was to test whether transfection of ventricular myocytes with inactive GSK3 beta would mimic preconditioning and whether a constitutively active form of GSK3 beta would prevent protection by an opioid receptor agonist. 2. Isolated ventricular myocytes from adult rats were infected with live adenovirus containing either a wild-type (wtGSK), constitutively active (caGSK) or dominant-negative (dnGSK) GSK3 beta plasmid. Cells were loaded with tetramethylrhodamine ethyl ester (TMRE) and exposed to H(2)O(2) (100 micromol/L) for 40 min before mitochondrial membrane potential (Delta Psi(m)) was assessed using flow cytometric analysis. 3. Fluorescence intensity was reduced in H(2)O(2)-treated cells compared with untreated cells, presumably because oxidant injury opened mitochondrial permeability transition pores, causing mitochondria to lose TMRE. The selective GSK3 beta inhibitor SB216763, as well as the delta-opioid receptor agonist [d-Ala(2)-D-Leu(5)]-enkephalin (DADLE) (1 micromol/L), protected cells against peroxide-induced loss of Delta Psi(m). 4. Cells transfected with dnGSK (1 micromol/L) were equally protected against peroxide stress, when given throughout the TMRE and H(2)O(2) treatment, confirming a protective effect of GSK3 beta with a highly selective inhibition. Cells transfected with wtGSK did not show any difference in responses to H(2)O(2), SB216763 or DADLE compared with untransfected cells, suggesting that adenovirus infection itself had no effect. In contrast, caGSK-transfected myocytes could no longer be protected with DADLE, suggesting a role for GSK3 beta between the surface receptor and the mitochondria. 5. These experiments confirm that inhibition of GSK3 beta protects the myocytes, but also that the preconditioning mimetic DADLE loses its protective effect when a constitutively active GSK3 beta is present.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1440-1681
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
684-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Inhibition of glycogen synthase kinase 3beta prevents peroxide-induced collapse of mitochondrial membrane potential in rat ventricular myocytes.
pubmed:affiliation
Department of Cardiology, Ernst-Moritz-Arndt University, Greifswald, Germany.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural