State Key Laboratory of Developmental Biology of Freshwater Fish, Protein Chemistry Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Toxins (Basel). 2021 Feb 12;13(2):136. doi: 10.3390/toxins13020136.
Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider 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.
拉托毒素-VI（LETX-VI）是一种新发现的蜘蛛卵中的肽神经毒素。为了探究 LETX-VI 对神经细胞的作用机制，采用下拉实验引导策略分析了 LETX-VI 对 PC12 细胞（一种常用的神经元模型）的影响。结果表明，LETX-VI 与 164 种 PC12 细胞蛋白相互作用，这些蛋白具有多种分子功能，如结合、催化、调节、结构活性等，从而广泛影响 PC12 细胞的生物学过程，特别是蛋白质代谢、对刺激的反应、物质运输和核酸代谢，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 增强了多巴胺的合成；正向调节细胞分裂和增殖；负向调节细胞周期阻滞、细胞死亡和细胞凋亡过程，因此对 PC12 细胞的细胞毒性有限，这一点在实验中得到了进一步证实。总的来说，LETX-VI 对 PC12 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，为进一步的相关研究提供了有价值的线索，包括帕金森病的相关研究。
