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(Circulation Research. 2001;89:750.)
© 2001 American Heart Association, Inc.

Reports

Antiischemic Effects of SB203580 Are Mediated Through the Inhibition of p38 Mitogen-Activated Protein Kinase

Evidence From Ectopic Expression of an Inhibition-Resistant Kinase

Jody L. Martin, Metin Avkiran, Roy A. Quinlan, Philip Cohen, Michael S. Marber

From the Department of Cardiology (J.L.M., M.A., M.S.M.), King’s College London, The Rayne Institute, St Thomas’ Hospital, London; the Department of Biological Sciences (R.A.Q.), University of Durham; and the MRC Protein Phosphorylation Unit (P.C.), Department of Biochemistry, University of Dundee, UK.

Correspondence to Mike Marber, Department of Cardiology, KCL, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK. E-mail mike.marber{at}kcl.ac.uk

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 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 p38 MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38 MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38 MAPK.

Key Words: SB203580 • p38 mitogen-activated protein kinase • preconditioning • isolated cells • signaling

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