N-type Ca v channel inhibition by spider venom peptide of Argiope bruennichi

[摘要] Background The spider venom is composed of various bioactive peptides and has well-known physiological characteristics, such as cytolytic and neurotoxic activities. However, there have been few studies on neurotoxic peptides derived from domestic indigenous spiders in Korea. Objective The study aimed to characterize and identify the venom peptide through genomic analysis from the domestic indigenous spider, Argiope bruennichi. Toxin-like peptides were selected using homology analysis against well-known toxin peptides along with the secondary structural characterization analysis by cysteine pattern and disulfide bonds. Modulation of voltage-gated calcium (Cav) channel was measured by Ca2+ influx using fluorescence dye. Results We found that a novel peptide Aranetoxin-Ab1a significantly reduced intracellular Ca2+ levels in human neuroblastoma cell line SH-SY5Y via the inactivation of N-type Cav channels. Decreased intracellular Ca2+ influx by the treatment of the peptide inactivated the extracellular-regulated protein kinase 1/2 and cAMP-response factor binding protein pathway. Conclusion Our results provide beneficial information for the potential development of drugs utilizing novel peptide derived from spider venom, showing the inhibition of N-type Cav by the peptide.

[关键词] Spider venom;Argiope bruennichi;Transcriptomics;RNA-sequencing;In silico analysis;Neurotoxicity