Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C
Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C
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DOI：
10.1523/jneurosci.22-03-00674.2002
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发表时间：
2002-02-01
影响因子：
5.3
通讯作者：
Klann, E
中科院分区：
文献类型：
--
作者：
Knapp, LT;Klann, E
最近的证据表明，活性氧（ROS），包括超氧化物，不仅是神经毒性，但作为小信使分子在正常的神经元过程，如突触可塑性。与这一想法相一致，我们表明，短暂孵育的海马切片与超氧化物生成系统黄嘌呤/黄嘌呤氧化酶（X/XO）在CA 1区产生了持久的增强突触传递。我们发现，X/XO诱导的增强与持续的超氧化物依赖性增加自主PKC活性，可以通过DEAE柱层析分离。X/XO诱导的增强作用被PKC的抑制所阻断，表明自主PKC活性的超氧化物依赖性增加是增强作用所必需的。我们还发现，X/XO诱导的增强和长时程增强（LTP）相互闭塞，这表明这些形式的可塑性共享相似的细胞机制。为了进一步支持这一观点，我们发现通过DEAE柱层析分离的自主PKC活性的持续的、超氧化物依赖性的增加也与LTP相关。两者合计，我们的研究结果表明，X/XO诱导的增强和LTP共享相似的细胞机制，包括自主PKC活性的超氧化物依赖性增加。最后，我们的研究结果表明，超氧化物，除了其众所周知的作用，作为一种神经毒素，也可以被认为是一个小的信使分子的正常神经信号的关键。
Recent evidence suggests that reactive oxygen species (ROS), including superoxide, are not only neurotoxic but function as small messenger molecules in normal neuronal processes such as synaptic plasticity. Consistent with this idea, we show that brief incubation of hippocampal slices with the superoxide-generating system xanthine/xanthine oxidase (X/XO) produces a long-lasting potentiation of synaptic transmission in area CA1. We found that X/XO-induced potentiation was associated with a persistent superoxide-dependent increase in autonomous PKC activity that could be isolated via DEAE column chromatography. The X/XO-induced potentiation was blocked by the inhibition of PKC, indicating that the superoxide-dependent increase in autonomous PKC activity was necessary for the potentiation. We also found that X/XO-induced potentiation and long-term potentiation (LTP) occluded one another, suggesting that these forms of plasticity share similar cellular mechanisms. In further support of this idea, we found that a persistent, superoxide-dependent increase in autonomous PKC activity isolated via DEAE column chromatography also was associated with LTP. Taken together, our findings indicate that X/XO-induced potentiation and LTP share similar cellular mechanisms, including superoxide-dependent increases in autonomous PKC activity. Finally, our findings suggest that superoxide, in addition to its well known role as a neurotoxin, also can be considered a small messenger molecule critical for normal neuronal signaling.