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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-5-28
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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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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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
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2828
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1998 Academic Press Limited.
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pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
383-92
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pubmed:dateRevised |
2010-1-15
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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
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pubmed:year |
1998
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pubmed:articleTitle |
Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning's anti-infarct effect in the rabbit heart.
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pubmed:affiliation |
Departments of Physiology and Medicine, College of Medicine, University of South Alabama, Mobile 36688, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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