MAP3K5 and ischemia: Myocardial ischemia is associated with a moderate increase in ROS and activation of p38-MAPKs but not JNKs, whereas redox stress increases substantially on reperfusion and this leads to activation of JNKs.9,29 Consistent with this, we detected ASK1 phosphorylation in perfused rat hearts subjected to ischemia and this phosphorylation, together with activation of p38-MAPKs, was suppressed by the ASK1 inhibitor, selonsertib (Figure 3B).