Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells.
Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells.
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Pull-Down 测定引导洞察 Latroeggtoxin-VI 对神经细胞的影响。
DOI：
10.3390/toxins13020136
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发表时间：
2021-02-12
期刊：
影响因子：
4.2
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Tang X;Yu D;Wang H;Meng W;Zhai Y;Lei Z;Liu Z;Wang X
Latroeggtoxin-VI（LETX-VI）是从蜘蛛L. tredecimguttatus。为了探索LETX-VI对神经细胞的作用机制，使用下拉分析指导策略分析LETX-VI对PC 12细胞（一种常用的神经元模型）的作用。LETX-VI显示与164种具有不同分子功能（如结合、催化、调节、结构活性等）的PC 12细胞蛋白相互作用，从而广泛影响PC 12细胞的生物学过程，特别是蛋白质代谢、对刺激的反应、物质转运和核酸代谢，分别有56.71%、42.07%、29.88%和28.66%的鉴定蛋白参与这些生物学过程。通过与相关蛋白相互作用，LETX-VI增强多巴胺的合成;正调节细胞分裂和增殖;负调节细胞周期停滞、细胞死亡和凋亡过程，因此对PC 12细胞具有有限的细胞毒性，这被进一步实验证实。一般而言，LETX-VI对PC 12细胞的作用更多是调节性的而不是细胞毒性的。这些发现加深了我们对LETX-VI对神经细胞作用机制的理解，并为包括帕金森病在内的进一步相关研究提供了有价值的线索。
Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider L. tredecimguttatus. To explore the mechanism of action of the LETX-VI on nerve cells, the effects of LETX-VI on PC12 cells, a commonly used neuron model, were analyzed using a pull-down assay-guided strategy. LETX-VI was shown to interact with 164 PC12 cell proteins that have diverse molecular functions such as binding, catalysis, regulation, structural activity, etc., thereby extensively affecting the biological processes in the PC12 cells, particularly protein metabolism, response to stimulus, substance transport, and nucleic acid metabolism, with 56.71%, 42.07%, 29.88% and 28.66% of the identified proteins being involved in these biological processes, respectively. By interacting with the relevant proteins, LETX-VI enhanced the synthesis of dopamine; positively regulated cell division and proliferation; and negatively regulated cell cycle arrest, cell death, and apoptotic processes, and therefore has limited cytotoxicity against the PC12 cells, which were further experimentally confirmed. In general, the effects of LETX-VI on PC12 cells are more regulatory than cytotoxic. These findings have deepened our understanding of the action mechanism of LETX-VI on nerve cells and provided valuable clues for further related researches including those on Parkinson’s disease.
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