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首页> 外文期刊>American Journal of Physiology >Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments.
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Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments.

机译：急性腺苷预处理是由离散的亚细胞区室中的p38 MAPK激活介导的。

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Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO i.v.), 2) the A(1)/A(2a) adenosine receptor AMP-579 (50 microg/kg i.v.), 3) AMP-579 + the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microg/kg i.v.), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg i.v.), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A(1) receptor PC.
机译：尽管已经建立了急性腺苷预处理（PC），但尚不清楚介导这种心脏保护作用的信号传导途径。由于腺苷受体激动剂激活p38 MAPK，并且该激酶与缺血性和药理性PC有关，因此本研究的目的是确定p38 MAPK在急性腺苷受体PC中的作用。还确定了p38 MAPK激活在缺血再灌注过程中离散的亚细胞区室中的作用。以下组用于体内大鼠缺血再灌注模型：1）对照（10％DMSO iv），2）A（1）/ A（2a）腺苷受体AMP-579（50 microg / kg iv）， 3）AMP-579 + A（1）受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX，100 microg / kg iv），4）AMP-579 + p38 MAPK抑制剂SB-203580（1 mg / kg iv）和5）单独使用SB-203580。通过蛋白质印迹分析在缺血前，缺血和再灌注时间点从心脏获得的胞浆，线粒体，膜和核/肌丝级分中测量p38 MAPK活化。使用AMP-579 PC观察到梗塞面积明显减少，DPCPX或SB-203580预处理阻止了这种作用。 AMP-579的治疗与缺血前核/肌丝级分中p38 MAPK活化的显着增加有关，而在缺血或再灌注期间未发生该激酶的活化。相反，在对照组中，p38 MAPK在局部缺血中被激活在线粒体部分中，并在再灌注中被激活在胞质，线粒体和膜部分中激活。 SB-203580阻止了AMP-579诱导的下游p38底物激活转录因子2磷酸化的增加。这些结果表明，p38 MAPK激活在急性腺苷A（1）受体PC的离散亚细胞区室中的作用。

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