Waxham M N, Grotta J C, Silva A J, Strong R, Aronowski J
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston 77225, USA.
J Cereb Blood Flow Metab. 1996 Jan;16(1):1-6. doi: 10.1097/00004647-199601000-00001.
Calcium/calmodulin-dependent protein kinase II (CaM-kinase) is a central enzyme in regulating neuronal processes. Imbalances in the activity and distribution of this enzyme have been reported following in vivo ischemia, and sustained decreases in activity correlate with subsequent neuronal death. In this report, mice that had been rendered deficient in the alpha subunit of CaM-kinase using gene knock-out technology were utilized to determine whether this enzyme is causally related to ischemic damage. Using a focal model of cerebral ischemia, we showed that homozygous knock-out mice lacking the alpha subunit exhibited an infarct volume almost twice that of wild-type litter mates. Heterozygous mice exhibited slightly less damage following ischemia than did homozygous mice, but infarct volumes remained significantly larger than those of wild-type litter mates. We conclude that reduced amounts of the alpha subunit of CaM-kinase predisposes neurons to increased damage following ischemia and that any perturbation that decreases the amount or activity of the enzyme will produce enhanced susceptibility to neuronal damage.
钙/钙调蛋白依赖性蛋白激酶II（CaM激酶）是调节神经元活动的关键酶。体内缺血后，该酶的活性和分布会出现失衡，其活性持续下降与随后的神经元死亡相关。在本报告中，我们利用基因敲除技术使CaM激酶α亚基缺失的小鼠，来确定该酶是否与缺血性损伤存在因果关系。使用局灶性脑缺血模型，我们发现缺乏α亚基的纯合敲除小鼠梗死体积几乎是野生型同窝小鼠的两倍。杂合小鼠缺血后的损伤比纯合小鼠略轻，但梗死体积仍显著大于野生型同窝小鼠。我们得出结论，CaM激酶α亚基数量减少会使神经元在缺血后更易受损，任何降低该酶数量或活性的干扰都会增加神经元对损伤的易感性。
