尼古丁
秀丽隐杆线虫
氧化应激
体内
神经毒性
活性氧
毒性
药理学
生物
转基因
RNA干扰
细胞生物学
化学
生物化学
神经科学
核糖核酸
遗传学
基因
有机化学
作者
Xiaoda Lu,Yue Zhang,Hongyuan Li,Yushan Jin,Lihui Zhao,Xiaohui Wang
标识
DOI:10.1016/j.neulet.2021.136114
摘要
Nicotine, a main active compound in tobacco, has been shown to attenuate amyloid-β (Aβ) mediated neurotoxicity. However, the detailed underlying mechanisms remains to be elucidated. In this study, nematode Caenorhabditis elegans (C. elegans) had been chosen as the model animal for dissecting the role of nicotine in the prevention of Aβ-induced toxicity in vivo.CL2120 and CL4176 transgenic worms of Alzheimer's disease (AD) models were treated with different concentrations of nicotine, and worm paralysis was monitored. Next, the effects of nicotine on Aβ deposits, Aβ oligomers, reactive oxygen species (ROS) and the oxidative stress resistance in worms were measured. Moreover, the pathway responsible for nicotine alleviating Aβ-induced toxicity in vivo was explored by observing the oxidative stress resistance of skn-1 or daf-16 mutants in the presence of nicotine. Furthermore, the worm paralysis and Aβ deposits were further checked in CL4176 worms with skn-1 RNA interference under the condition of nicotine.Nicotine (5 μM) attenuated AD-like symptoms of worm paralysis in CL2120 and CL4176 transgenic C. elegans. Nicotine did not inhibit Aβ aggregation in vitro, however it suppressed Aβ deposits and reduced the Aβ oligomers to alleviate the toxicity induced by Aβ overexpression in C. elegans. Although nicotine did not possess apparent intrinsic anti-oxidative activity, it decreased in vivo reactive oxygen species (ROS). Nicotine enhanced the oxidative stress resistance of C. elegans, which was mediated by SKN-1 but not DAF-16 signaling. Furthermore, skn-1 RNAi abrogated the effect of nicotine reducing Aβ deposits in vivo and completely blocked nicotine preventing Aβ induced worm paralysis.Nicotine reduces Aβ oligomer formation and alleviates Aβ-induced paralysis of C. elegans, which is mediated by SKN-1 signaling.
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