State Key Laboratory of Developmental Biology of Freshwater Fish, Protein Chemistry Laboratory, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
J Biochem Mol Toxicol. 2021 Aug;35(8):e22825. doi: 10.1002/jbt.22825. Epub 2021 May 28.
Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin discovered from Latrodectus tredecimguttatus eggs. In the current study, the action features of the neurotoxin on PC12 cells were systematically investigated. LETX-VI could promote dopamine release from PC12 cells in the absence and presence of Ca2+, involving an even more complex action mechanism in the presence of Ca2+ and when the treatment time was longer. Although LETX-VI enchanced the autophagy and secretion activity in PC 12 cells, it showed no remarkable influence on the proliferation, cell cycle, apoptosis and ultrastructure of the cells. Pulldown combined with CapLC-MS/MS analysis suggested that LETX-VI affected PC12 cells by interacting with multiple proteins involved in the metabolism, transport, and release of neurotransmitters, particularly dopamine. The low cytotoxicity and effective regulatory action of LETX-VI on PC12 cells suggest the potential of the active peptide in the development of drugs for the treatment of some dopamine-related psychotic diseases and cancers.
Latroeggtoxin-VI（LETX-VI）是一种从Latrodectus tredecimguttatus 卵中发现的肽神经毒素。在本研究中，系统研究了该神经毒素对 PC12 细胞的作用特征。LETX-VI 可在无 Ca2+和有 Ca2+的情况下促进 PC12 细胞中多巴胺的释放，在有 Ca2+且作用时间更长的情况下，涉及更复杂的作用机制。虽然 LETX-VI 增强了 PC12 细胞中的自噬和分泌活性，但对细胞的增殖、细胞周期、凋亡和超微结构没有显著影响。下拉联合 CapLC-MS/MS 分析表明，LETX-VI 通过与参与神经递质代谢、转运和释放的多种蛋白质相互作用来影响 PC12 细胞，特别是多巴胺。LETX-VI 对 PC12 细胞的低细胞毒性和有效调节作用表明，该活性肽在开发治疗一些与多巴胺相关的精神病和癌症的药物方面具有潜力。
