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 reperfu sion (ischemia/reperfusion) in the rat heart and kidney, We observe th e activation of three stress-inducible mitogen-activated protein (MAP) kinases in these tissues: p38 MAP kinase and the 46- and 55-kDa isofo rms of Jun N-terminal kinase (JNK(46) and JNK(55)). The heart and kidn ey show distinct time courses in the activation of p38 MAP kinase duri ng 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 k idney all three kinases are active. We also examined the expression pa ttern of two stress-responsive genes, c-Jun and ATF3. Our results indi cate that in the heart both genes are induced by ischemia and ischemia /reperfusion. However, in the kidney c-Jun and ATF3 expression is indu ced only by ischemia/reperfusion. To correlate these molecular events with tissue damage we examined DNA laddering, a common marker of apopt osis. A significant increase in DNA laddering was evident in both hear t and kidney following ischemia/reperfusion and correlated with the pa ttern of kinase activation, supporting a link between stress kinase ac tivation and apoptotic cell death in these tissues.