Biochemical and cytotoxic evaluation of latroeggtoxin-VI against PC12 cells

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.