Hara H, Onodera H, Yoshidomi M, Matsuda Y, Kogure K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
J Cereb Blood Flow Metab. 1990 Sep;10(5):646-53. doi: 10.1038/jcbfm.1990.117.
The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1-10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.
在海马体CA1亚区研究了蛋白激酶抑制剂和一种钙调蛋白激酶抑制剂（W-7）对缺血性神经元损伤的保护作用。星形孢菌素、KT5720和KT5822分别用作蛋白激酶C（PKC）、环磷酸腺苷依赖性蛋白激酶和环磷酸鸟苷依赖性蛋白激酶的抑制剂。所有测试化合物均局部注射到海马体CA1亚区。在沙鼠缺血模型中，缺血前30分钟给予星形孢菌素（0.1 - 10纳克）可剂量依赖性地预防神经元损伤。然而，即使剂量为10纳克，KT5720、KT5822和W-7也无效。在大鼠缺血模型中，缺血前给予星形孢菌素（10纳克）也可预防神经元损伤，尽管再灌注后10或180分钟给予星形孢菌素无效。这些结果表明PKC参与了缺血后CA1锥体细胞的死亡，并且在早期再灌注期，通过PKC介导的过程，脆弱的CA1锥体细胞的命运可能会被决定。
