Sato M, Cordis G A, Maulik N, Das D K
Cardiovascular Research Center, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110, USA.
Am J Physiol Heart Circ Physiol. 2000 Sep;279(3):H901-7. doi: 10.1152/ajpheart.2000.279.3.H901.
The role of stress-activated protein kinases (SAPKs), c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase, in preconditioning (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 microM curcumin, a c-Jun and JNK1 inhibitor, or 5 microM SB 203580, a p38 MAP kinase inhibitor. Another group of hearts was preperfused with 20 microM anisomycin, a stimulator for both JNK and p38 MAP kinases. I/R increased the protein levels of JNK1, c-Jun, and p38 MAP kinase. PC also enhanced the induction 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 protein levels, whereas it had no effects on p38 MAP kinase. SB 203580, on the other hand, was equally effective in reducing the p38 MAP kinase activation but exerted no effects on JNK1 and c-Jun induction. I/R-mediated increased myocardial infarction was reduced by any of the following compounds: anisomycin, curcumin, and SB 203580. The cardioprotective effects of PC were abolished by either curcumin or SB 203580. The results demonstrate that PC is mediated by a signal-transduction pathway involving both JNK1 and p38 MAP kinase. Activation of SAPKs, although transient, is obligatory for PC.
利用离体大鼠心脏，通过进行四个循环周期（每个周期为5分钟缺血和10分钟再灌注，随后是30分钟缺血和2小时再灌注（I/R）），研究了应激激活蛋白激酶（SAPK）、c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白（MAP）激酶在预处理（PC）中的作用。一组心脏预先灌注100微摩尔姜黄素（一种c-Jun和JNK1抑制剂）或5微摩尔SB 203580（一种p38 MAP激酶抑制剂）。另一组心脏预先灌注20微摩尔茴香霉素（一种JNK和p38 MAP激酶的刺激剂）。I/R增加了JNK1、c-Jun和p38 MAP激酶的蛋白水平。PC也增强了这些激酶的诱导，但随后I/R介导的增加被PC阻断。姜黄素阻断了I/R和PC介导的JNK1和c-Jun蛋白水平的增加，而对p38 MAP激酶没有影响。另一方面，SB 203580在降低p38 MAP激酶激活方面同样有效，但对JNK1和c-Jun诱导没有影响。以下任何一种化合物均可减少I/R介导的心肌梗死增加：茴香霉素、姜黄素和SB 203580。姜黄素或SB 203580均可消除PC的心脏保护作用。结果表明，PC是由涉及JNK1和p38 MAP激酶的信号转导途径介导的。SAPK的激活虽然是短暂的，但对PC是必不可少的。
