SUMMARYWe investigated the activation of three subfamilies of MAPKs (ERK, JNKs and p38-MAPK) by oxidative stress in the isolated perfused amphibian heart. Activation of p43-ERK by 100 μmol l-1 H2O2was maximally observed within 5 min, remained elevated for 30 min and was comparable with the effect of 1 μmol l-1 PMA. p43-ERK activation by H2O2 was inhibited by PD98059 but not by SB203580. The p46 and p52 species of JNKs were maximally activated by 2.5- and 2.1-fold,respectively, by 100 μmol l-1 H2O2 within 2 min. JNK activation was still detectable after 15 min, reaching control values at 30 min of treatment. p38-MAPK was maximally activated by 9.75-fold by 100 μmol l-1 H2O2 after 2 min and this activation progressively declined thereafter, reaching control values within 45 min of treatment. The observed dose-dependent profile of p38-MAPK activation by H2O2 revealed that 30 μmol l-1 H2O2 induced maximal phosphorylation,whereas 100–300 μmol l-1 H2O2induced considerable activation of the kinase. Our studies also showed that the phosphorylation of MAPKAPK2 by H2O2 followed a parallel time-dependent pattern and that SB203580 abolished this phosphorylation. Furthermore, our experiments clearly showed that 30 μmol l-1 H2O2 induced a strong, specific phosphorylation of HSP27. Our immunohistochemical studies showed that immune complexes of phosphorylated forms of both p38-MAPK and HSP27 were strongly enhanced by 30 μmol l-1 H2O2 in the perinuclear region as well as dispersedly in the cytoplasm of ventricular cells and that SB203580 abolished this phosphorylation. These data indicate that oxidative stress is a powerful activator of all three MAPK subfamilies in the amphibian heart. Stimulation of p38-MAPK and the consequent phosphorylation of HSP27 may be important in cardioprotection under such conditions.
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