STAUROSPORINE, A NOVEL PROTEIN-KINASE-C INHIBITOR, PREVENTS POSTISCHEMIC NEURONAL DAMAGE IN THE GERBIL AND RAT
STAUROSPORINE, A NOVEL PROTEIN-KINASE-C INHIBITOR, PREVENTS POSTISCHEMIC NEURONAL DAMAGE IN THE GERBIL AND RAT
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DOI：
10.1038/jcbfm.1990.117
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发表时间：
1990-09-01
影响因子：
6.3
通讯作者：
KOGURE, K
中科院分区：
文献类型：
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作者：
HARA, H;ONODERA, H;KOGURE, K
在海马 CA1 亚区检查了蛋白激酶抑制剂和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。 Staurosporine、KT5720 和 KT5822 分别用作蛋白激酶 C (PKC)、环 AMP 依赖性蛋白激酶和环 GMP 依赖性蛋白激酶的抑制剂。将所有测试化合物局部注射到海马的 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 ng），以剂量依赖性方式预防神经元损伤。然而，KT5720、KT5822 和 W-7 即使剂量为 10 ng 也无效。在大鼠缺血模型中，在缺血性损伤之前施用星形孢菌素（10 ng）也可以预防神经元损伤，尽管在再循环后 10 或 180 分钟施用星形孢菌素无效。这些结果表明 PKC 参与缺血后 CA1 锥体细胞死亡，并且可以在早期再循环期间确定通过 PKC 介导的过程脆弱的 CA1 锥体细胞的命运。
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.