Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-5-28
pubmed:abstractText
The present study tested the hypothesis that one or more tyrosine kinase(s) are downstream of protein kinase C (PKC) in the signal transduction pathway responsible for the cardioprotective effect of ischemic preconditioning (PC). Isolated rabbit hearts were subjected to 30 min of regional ischemia followed by 2 h of reperfusion. Infarct size was measured by triphenyltetrazolium staining and expressed as a percentage of the area at risk. Infarction in control hearts was 32.9+/-1.8%. Ischemic PC with 5-min ischemia/10-min reperfusion reduced infarct size to 11.5+/-1.5% (P<0.05). Infusion of the tyrosine kinase inhibitors, genistein (50 microM) or lavendustin A (0.5 microM), alone did not affect the level of infarction. When infused around the 5-min PC ischemia genistein failed to block protection (13.7+/-1.0%). However, when present at the onset of the 30-min ischemia both genistein and lavendustin A completely aborted protection (31.4+/-2.0 and 28.1+/-1.5%, respectively). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 0.05 nmol) was as protective is ischemic PC (14.9+/-3.0%; P<0. 05). Similar to PC, PMA-induced protection was completely prevented by both genistein and lavendustin A. Conversely, anisomycin (50 ng/ml), an activator of MAP kinase kinases (dual tyrosine and threonine kinases), was very protective (7.5+/-1.6%; P<0.05) and this protection was still present when PKC was inhibited by 5 microM chelerythrine (12.1+/-1.6%; P<0.05). In conclusion, activation of a tyrosine kinase during the long ischemia appears to be required for cardioprotection in the rabbit heart. Furthermore, the ability of tyrosine kinase inhibitors to block PMA-induced protection in conjunction with the failure of PKC inhibition to prevent anisomycin-induced protection suggests that the tyrosine kinase is downstream of PKC and that the tyrosine kinase may be a MAP kinase kinase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids, http://linkedlifedata.com/resource/pubmed/chemical/Anisomycin, http://linkedlifedata.com/resource/pubmed/chemical/Benzophenanthridines, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Genistein, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/Phenanthridines, http://linkedlifedata.com/resource/pubmed/chemical/Phenols, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/chelerythrine, http://linkedlifedata.com/resource/pubmed/chemical/lavendustin A
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press Limited.
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-92
pubmed:dateRevised
2010-1-15
pubmed:meshHeading
pubmed-meshheading:9515015-Alkaloids, pubmed-meshheading:9515015-Animals, pubmed-meshheading:9515015-Anisomycin, pubmed-meshheading:9515015-Benzophenanthridines, pubmed-meshheading:9515015-Enzyme Activation, pubmed-meshheading:9515015-Enzyme Inhibitors, pubmed-meshheading:9515015-Female, pubmed-meshheading:9515015-Genistein, pubmed-meshheading:9515015-Hemodynamics, pubmed-meshheading:9515015-Ischemic Preconditioning, Myocardial, pubmed-meshheading:9515015-Male, pubmed-meshheading:9515015-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:9515015-Myocardial Infarction, pubmed-meshheading:9515015-Myocardial Reperfusion Injury, pubmed-meshheading:9515015-Phenanthridines, pubmed-meshheading:9515015-Phenols, pubmed-meshheading:9515015-Protein Kinase C, pubmed-meshheading:9515015-Protein Kinases, pubmed-meshheading:9515015-Protein-Tyrosine Kinases, pubmed-meshheading:9515015-Rabbits, pubmed-meshheading:9515015-Signal Transduction, pubmed-meshheading:9515015-Tetradecanoylphorbol Acetate
pubmed:year
1998
pubmed:articleTitle
Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning's anti-infarct effect in the rabbit heart.
pubmed:affiliation
Departments of Physiology and Medicine, College of Medicine, University of South Alabama, Mobile 36688, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.