SAPKs regulation of ischemic preconditioning

The role of stress-activated protein kinases (SAPKs), c-Jun NH2-terminal ki nase (JNK) and p38 mitogen-activated protein (MAP) kinase, in preconditioni ng (PC) was examined with the use of isolated rat hearts subjected to four cyclic episodes of 5-min ischemia and 10-min reperfusion followed by 30-min ischemia and 2-h reperfusion (I/R). A group of hearts was preperfused with 100 mu M curcumin, a c-Jun and JNK1 inhibitor, or 5 mu M SB 203580, a p38 MAP kinase inhibitor. Another group of hearts was preperfused with 20 mu M anisomycin, a stimulator for both JNK and p38 MAP kinases. I/R increased th e protein levels of JNK1, c-Jun, and p38 MAP kinase. PC also enhanced the i nduction of these kinases, but subsequent I/R-mediated increase was blocked by PC. Curcumin blocked I/R- and PC-mediated increase in JNK1 and c-Jun pr otein levels, whereas it had no effects on p38 MAP kinase. SB 203580, on th e other hand, was equally effective in reducing the p38 MAP kinase activati on but exerted no effects on JNK1 and c-Jun induction. I/R-mediated increas ed myocardial infarction was reduced by any of the following compounds: ani somycin, curcumin, and SB 203580. The cardioprotective effects of PC were a bolished by either curcumin or SB 203580. The results demonstrate that PC i s mediated by a signal-transduction pathway involving both JNK1 and p38 MAP kinase. Activation of SAPKs, although transient, is obligatory for PC.