Abstract
The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the alpha isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart-derived cells and adult rat cardiocytes expressing wild-type p38alpha MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38alpha MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38alpha MAPK.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenoviridae / genetics
-
Animals
-
Animals, Newborn
-
Binding Sites / drug effects
-
Binding Sites / genetics
-
Cell Survival / drug effects
-
Cells, Cultured
-
Drug Resistance / genetics
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology*
-
Genetic Vectors / genetics
-
Genetic Vectors / pharmacology
-
Imidazoles / pharmacology*
-
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
Mitogen-Activated Protein Kinases / genetics
-
Mitogen-Activated Protein Kinases / metabolism
-
Mutagenesis, Site-Directed
-
Myocardial Ischemia / drug therapy*
-
Myocardial Ischemia / enzymology
-
Myocardium / cytology
-
Myocardium / enzymology
-
Pyridines / pharmacology*
-
Rats
-
Reperfusion Injury / enzymology
-
Reperfusion Injury / prevention & control*
-
p38 Mitogen-Activated Protein Kinases
Substances
-
Enzyme Inhibitors
-
Imidazoles
-
Pyridines
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
SB 203580