Chronic Sodium Valproate Selectively Decreases Protein Kinase C α and ε In Vitro
Chronic Sodium Valproate Selectively Decreases Protein Kinase C α and ε In Vitro
复制标题
慢性丙戊酸钠在体外选择性降低蛋白激酶 C α 和 ε
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
W. Potter
中科院分区：
文献类型：
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作者：
Guang Chen;H. Manji;D. B. Hawver;C. Wright;W. Potter
摘要：丙戊酸（VPA）是一种脂肪酸抗癫痫药，具有抗躁狂特性，但其治疗功效的分子机制仍有待阐明。鉴于越来越多的证据表明一线抗躁狂药物锂对蛋白激酶 C (PKC) 的影响，我们研究了 VPA 对该酶各个方面的影响。大鼠 C6 神经胶质瘤细胞长期暴露于“治疗”浓度（0.6 mM）的 VPA 中（6-7 天）会导致膜和细胞质部分中的 PKC 活性降低，并增加 PKC 活性的细胞质/膜比率。蛋白质印迹分析显示，长期暴露于 VPA 后，膜和胞质部分中的 PKC α 和 ε（但不是 δ 或 ζ）水平发生同工酶选择性降低；添加到反应混合物中的 VPA 不会改变 PKC 活性或 3H-佛波酯结合。总之，这些数据表明，慢性 VPA 间接降低了 C6 细胞中 PKC 特定同工酶的水平。鉴于 PKC 在调节神经元信号转导和调节神经递质系统之间的细胞内串扰中的关键作用，PKC α 和 ε 的特异性降低可能在 VPA 的抗躁狂作用中发挥作用。
Abstract: Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first‐line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6–7 days) of rat C6 glioma cells to “therapeutic” concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme‐selective decreases in the levels of PKC α and ε (but not δ or ζ) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or 3H‐phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross‐talk between neurotransmitter systems, the specific decreases in PKC α and ε may play a role in the antimanic effects of VPA.
影响因子：
2.7
作者：
Cohen, G;Rubinstein, S;Breitbart, H
通讯作者：
Breitbart, H