Activation of protein kinase A and C prevents recovery from persistent depolarization produced by oxygen and glucose deprivation in rat hippocampal neurons.
Activation of protein kinase A and C prevents recovery from persistent depolarization produced by oxygen and glucose deprivation in rat hippocampal neurons.
复制标题
蛋白激酶 A 和 C 的激活可防止大鼠海马神经元因缺氧和缺糖而产生的持续去极化恢复。
DOI：
10.1152/jn.00537.2011
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发表时间：
2012
影响因子：
2.5
通讯作者：
E. Tanaka
中科院分区：
文献类型：
--
作者：
Y. Murai;Y. Okabe;E. Tanaka
在大鼠脑片上对大鼠海马CA 1区神经元进行细胞内记录，以研究cAMP依赖性蛋白激酶（PKA）和钙/磷脂依赖性蛋白激酶C（PKC）是否参与了氧和葡萄糖剥夺（OGD）诱导的膜功能障碍。氧和葡萄糖剥夺培养基的灌流在灌流开始后105分钟产生快速去极化。当在快速去极化后立即重新引入氧气和葡萄糖时，膜进一步去极化（持续去极化），并在重新引入5分钟后达到0 mV。用PKA抑制剂H-89和Rp-cAMPS以及腺苷酸环化酶抑制剂SQ 22，536对切片制备物进行预处理，在以浓度依赖性方式重新引入氧气和葡萄糖后，膜显著恢复到暴露前的电位水平。另一方面，磷脂酶C抑制剂，U 73122，PKC抑制剂，GF 109203 X，和非选择性蛋白激酶抑制剂，staurosporine，也显着恢复膜后重新引入。此外，肌醇-1，4，5-三磷酸受体拮抗剂2-氨基乙基二苯基硼酸酯和钙调蛋白抑制剂三氟拉嗪和W-7在重新引入后显著恢复了膜，而刺激性G蛋白的α亚基选择性拮抗剂NF 449、Ca（2+）/钙调蛋白依赖性激酶II抑制剂KN-62和肌球蛋白轻链激酶抑制剂ML-7均未恢复膜。在重新引入后显著恢复了膜。这些结果表明，PKA和/或PKC的激活阻止了从OGD产生的持续去极化的恢复。Ca（2+）/钙调素刺激的腺苷酸环化酶可能参与PKA的激活。
Intracellular recordings were made from rat hippocampal CA1 neurons in rat brain slice preparations to investigate whether cAMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase C (PKC) contribute to the membrane dysfunction induced by oxygen and glucose deprivation (OGD). Superfusion of oxygen- and glucose-deprived medium produced a rapid depolarization ∼5 min after the onset of the superfusion. When oxygen and glucose were reintroduced immediately after the rapid depolarization, the membrane depolarized further (persistent depolarization) and reached 0 mV after 5 min from the reintroduction. The pretreatment of the slice preparation with PKA inhibitors, H-89 and Rp-cAMPS, and an adenylate cyclase inhibitor, SQ 22, 536, significantly restored the membrane toward the preexposure potential level after the reintroduction of oxygen and glucose in a concentration-dependent manner. On the other hand, a phospholipase C inhibitor, U73122, a PKC inhibitor, GF109203X, and a nonselective protein kinase inhibitor, staurosporine, also significantly restored the membrane after the reintroduction. Moreover, an inositol-1,4,5-triphosphate receptor antagonist, 2-aminoethyl diphenylborinate, and calmodulin inhibitors, trifluoperazine and W-7, significantly restored the membrane after the reintroduction, while neither an α-subunit-selective antagonist for stimulatory G protein, NF449, a Ca(2+)/calmodulin-dependent kinase II inhibitor, KN-62, nor a myosin light chain kinase inhibitor, ML-7, significantly restored the membrane after the reintroduction. These results suggest that the activation of PKA and/or PKC prevents the recovery from the persistent depolarization produced by OGD. The Ca(2+)/calmodulin-stimulated adenylate cyclase may contribute to the activation of PKA.
影响因子：
50.3
作者：
Kau, TR;Schroeder, F;Silver, PA
通讯作者：
Silver, PA