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Antiischemic Effects of SB203580 Are Mediated Through the Inhibition of p38α Mitogen-Activated Protein Kinase

2001; Lippincott Williams & Wilkins; Volume: 89; Issue: 9 Linguagem: Inglês

10.1161/hh2101.099504

1524-4571

Joel W. Martin, Metin Avkiran, Roy A. Quinlan, Philip Cohen, Michael Marber,

Cell death mechanisms and regulation

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 α 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 p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.