Zalewska T, Zabłocka B, Domańska-Janik K
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Acta Neurobiol Exp (Wars). 1996;56(1):41-8. doi: 10.55782/ane-1996-1102.
Transient cerebral ischemia induces, besides delayed neurodegeneration in selected brain structures, a number of early responses which may mediate ischemic injury/repair processes. Here we report that 5 min exposure to cerebral ischemia in gerbils induces a rapid inhibition and subsequent translocation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). These changes were partially reversible during a 24 h post-ischemic recovery. Concomitantly the total amount of the enzyme protein, as revealed by Western blotting (alpha-subunit specific), remained stable. This is consistent with our previous hypothesis, that the mechanism of ischemic CaMKII down-regulation involves a reversible posttranslational modification-(auto)phosphorylation, rather than the degradation of enzyme protein. The effectiveness of known modulators of post-ischemic outcome in counteracting CaMKII inhibition was tested. Three of these drugs, namely dizocilpine (MK-801), N-nitro-L-arginine methyl ester (L-NAME) and ginkgolide (BN52021), all significantly attenuated the enzyme response to ischemia, whereas an obvious diversity in the time-course of their actions implicates different mechanisms involved.
短暂性脑缺血除了会在特定脑结构中引发延迟性神经退行性变外，还会引发一些早期反应，这些反应可能介导缺血性损伤/修复过程。在此我们报告，沙鼠脑部缺血5分钟会诱导钙/钙调蛋白依赖性蛋白激酶II（CaMKII）迅速受到抑制并随后发生易位。这些变化在缺血后24小时的恢复过程中部分可逆。同时，通过蛋白质印迹法（α亚基特异性）显示，酶蛋白的总量保持稳定。这与我们之前的假设一致，即缺血性CaMKII下调的机制涉及可逆的翻译后修饰——（自身）磷酸化，而非酶蛋白的降解。我们测试了已知的缺血后结果调节剂在对抗CaMKII抑制方面的有效性。其中三种药物，即地佐环平（MK-801）、N-硝基-L-精氨酸甲酯（L-NAME）和银杏内酯（BN52021），均显著减弱了该酶对缺血的反应，而它们作用的时间进程存在明显差异，这表明涉及不同的机制。
