Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.
Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.
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果蝇脱帽蛋白 2 的下调介导慢性尼古丁暴露诱导的运动亢进
DOI：
10.1371/journal.pone.0052521
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Guo A
中科院分区：
文献类型：
--
作者：
Ren J;Sun J;Zhang Y;Liu T;Ren Q;Li Y;Guo A
长期使用烟草会通过调节多种基因引起尼古丁依赖，并伴随着各种健康问题。对哺乳动物系统的研究揭示了尼古丁影响的一些关键因素，包括烟碱乙酰胆碱受体（nAChR）、多巴胺和其他神经递质。然而，尼古丁诱导的分子和行为改变之间的信号通路仍然难以捉摸。利用慢性尼古丁给药模式，我们发现，成年雄性果蝇表现出运动过度活跃后，连续三天的尼古丁暴露，而尼古丁幼稚的苍蝇没有。引人注目的是，这种慢性尼古丁诱导的运动过度活跃（cNILH）被废除在脱帽蛋白2或1（Dcp 2或Dcp 1）缺陷的苍蝇，而只有Dcp 2缺陷的苍蝇表现出更高的基础水平的运动活动比对照组。这些结果表明，Dcp 2在慢性尼古丁暴露的反应中起着关键作用。此外，果蝇头中Dcp 2的信使RNA（mRNA）水平被慢性尼古丁处理抑制，神经系统中Dcp 2表达的上调阻断了cNILH。这些结果表明，Dcp 2的下调介导慢性尼古丁暴露诱导的运动功能亢进的果蝇。脱帽蛋白在mRNA降解中起主要作用;然而，它们在神经系统中的功能很少被研究。我们的研究结果揭示了一个显着的作用，mRNA decapping通路在发展中的运动过度活跃，响应于慢性尼古丁暴露，并确定Dcp 2作为一个潜在的候选人，为未来的尼古丁依赖的研究。
Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.
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影响因子：
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