Biochemical and cytotoxic evaluation of latroeggtoxin-VI against PC12 cells
Biochemical and cytotoxic evaluation of latroeggtoxin-VI against PC12 cells
复制标题
LatroeggtoxinⅥ 对 PC12 细胞的生化和细胞毒性评价
DOI：
10.1002/jbt.22825
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发表时间：
2021-05-28
影响因子：
3.6
通讯作者：
Wang，Xianchun
中科院分区：
文献类型：
--
作者：
Tang，Xiaochao;Yu，Dianmei;Wang，Xianchun
Latrodectus tredecimguttatus Latrodectus latoeggtoxin‐VI （LETX‐VI）是一种从Latrodectus tredecimguttatus卵中发现的多肽神经毒素。本研究系统地研究了神经毒素对PC12细胞的作用特征。LETX‐VI可以在Ca2+存在和不存在的情况下促进PC12细胞释放多巴胺，在Ca2+存在和处理时间较长的情况下，其作用机制更为复杂。LETX‐VI虽然增强了pc12细胞的自噬和分泌活性，但对细胞的增殖、细胞周期、凋亡和超微结构无显著影响。Pulldown联合CapLC - MS/MS分析表明，LETX - VI通过与参与神经递质（尤其是多巴胺）代谢、运输和释放的多种蛋白相互作用影响PC12细胞。LETX - VI对PC12细胞的低细胞毒性和有效的调节作用表明，该活性肽在治疗一些多巴胺相关精神病和癌症的药物开发中具有潜力。
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.