Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney

In this report we investigate the molecular mechanisms that contribute to tissue damage following ischemia and ischemia coupled with reperfusion (ischemia/reperfusion) in the rat heart and kidney, We observe the activation of three stress-inducible mitogen-activated protein (MAP) kinases in these tissues: p38 MAP kinase and the 46- and 55-kDa isoforms of Jun N-terminal kinase (JNK(46) and JNK(55)). The heart and kidney show distinct time courses in the activation of p38 MAP kinase during ischemia but no activation of either JNK(46) or JNK(55). These two tissues also respond differently to ischemia/reperfusion. In the heart we observe activation of JNK(55) and p38 MAP kinase, whereas in the kidney all three kinases are active. We also examined the expression pattern of two stress-responsive genes, c-Jun and ATF3. Our results indicate that in the heart both genes are induced by ischemia and ischemia/reperfusion. However, in the kidney c-Jun and ATF3 expression is induced only by ischemia/reperfusion. To correlate these molecular events with tissue damage we examined DNA laddering, a common marker of apoptosis. A significant increase in DNA laddering was evident in both heart and kidney following ischemia/reperfusion and correlated with the pattern of kinase activation, supporting a link between stress kinase activation and apoptotic cell death in these tissues.