Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Antimicrobial peptides (AMPs) are crucial components of the innate immune system, exhibiting broad-spectrum antimicrobial activity.
• While AMPs' effects on prokaryotes are well-studied, their mechanisms of action on eukaryotic cells, particularly their cytotoxic properties, remain largely unclear.
• Novel cationic AMPs, Smp24 and Smp43, were isolated from Egyptian scorpion (Scorpio maurus palmatus) venom.

Purpose of the Study:

• To investigate the cytotoxic effects of Smp24 and Smp43 on human acute leukemia cell lines (KG1-a, CCRF-CEM) and non-tumorigenic cell lines (CD34+, HRECs, HaCaT).
• To elucidate the molecular mechanisms underlying the cytotoxicity of these scorpion-derived AMPs in eukaryotic cells.

Main Methods:

• Cell viability assays were performed on various human cell lines exposed to Smp24 and Smp43.
• Gene expression analysis focused on caspase-1 and downstream interleukin-1β (IL-1β) following peptide treatment.
• Transmission electron microscopy (TEM) was employed to examine ultrastructural changes in treated cells.

Main Results:

• Smp24 and Smp43 exhibited dose-dependent cytotoxicity against all tested cell lines, with HaCaT cells showing reduced sensitivity.
• Caspase-1 gene expression was uniquely upregulated in all cell lines except HaCaT, accompanied by increased IL-1β expression across all lines.
• TEM revealed characteristic pyroptotic features, including membrane blebbing, autolysosome formation, and lipid droplets, with unique glycogen deposits in KG1-a cells.

Conclusions:

• Scorpion venom AMPs Smp24 and Smp43 possess significant cytotoxic potential against both cancerous and non-cancerous human cells.
• These peptides trigger a novel cell death pathway involving caspase-1 activation and IL-1β release, characteristic of pyroptosis.
• The findings provide new insights into the mechanisms of scorpion AMPs and their potential therapeutic applications.