Oxidation of a potassium channel causes progressive sensory function loss during aging.
Oxidation of a potassium channel causes progressive sensory function loss during aging.
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DOI：
10.1038/nn.2291
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发表时间：
2009-05
影响因子：
25
通讯作者：
Sesti, Federico
中科院分区：
文献类型：
--
作者：
Cai, Shi-Qing;Sesti, Federico
一个核心问题是钾 (K+) 通道（神经元兴奋性的关键调节因子）是否是活性氧 (ROS) 的目标，以及这些相互作用是否在神经退行性疾病的机制中发挥作用。在这里，我们发现，衰老过程中 K+ 通道 KVS-1 的氧化会导致秀丽隐杆线虫的感觉功能丧失，而保护该通道免受氧化可以保护神经元功能。趋化性是由 KVS-1 控制的功能，在暴露于氧化剂的蠕虫中显着受损，但在含有抗氧化 KVS-1 突变体 (C113S) 的蠕虫中仅受到中度影响。在衰老的 C113S 转基因蠕虫中，自由基积累的影响与野生型相比显着减弱。电生理学分析表明，衰老过程中 ROS 的积累或急性暴露于氧化剂，主要作用是改变介导趋化性的神经元的兴奋性。总之，这些发现确立了 ROS 介导的电压门控 K+ 通道氧化在无脊椎动物衰老过程中感觉衰退中的关键作用。
A central question is whether potassium (K+) channels, which are key regulators of neuronal excitability, are targets of reactive oxygen species (ROS) and whether these interactions have a role in the mechanisms underlying neurodegeneration. Here, we show that oxidation of K+ channel KVS-1 during ageing causes sensory function loss in Caenorhabditis elegans, and that protection of this channel from oxidation preserves neuronal function. Chemotaxis, a function controlled by KVS-1, was significantly impaired in worms exposed to oxidizing agents, but only moderately affected in worms harboring an oxidation-resistant KVS-1 mutant (C113S). In ageing C113S transgenic worms, the effects of free radical accumulation were significantly attenuated compared to wild type. Electrophysiological analyses showed that both ROS accumulation during ageing, or acute exposure to oxidizing agents, acted primarily to alter the excitability of the neurons that mediate chemotaxis. Together, these findings establish a pivotal role for ROS-mediated oxidation of voltage-gated K+ channels in sensorial decline during ageing in invertebrates.
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影响因子：
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作者：
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发表时间：
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影响因子：
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