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Heterodimeric vipoxin and its individual monomeric subunits display a dynamic structure-function relationship on RPE
Yulia Petsevа1, Kirilka Mladenova1, Maria Ganeva1
1Sofia University "St. Kliment Ohridski", Faculty of Biology, Department of Biochemistry, Sofia, Bulgaria.
Archives of Biochemistry and Biophysics
|February 20, 2025
Summary
Snake venom phospholipase A2 (svPLA2) subunits, vipoxin basic component (VBC) and vipoxin acidic component (VAC), exhibit distinct cytotoxic and genotoxic effects on retinal pigment epithelial cells. Their interactions dictate varied biological activities based on cell microenvironment.
Area of Science:
- Toxicology
- Molecular Biology
- Cell Biology
Background:
- Snake venom phospholipases A2 (svPLA2) are potent toxins with diverse catalytic and non-catalytic activities.
- Vipoxin, a heterodimeric neurotoxin from Vipera ammodytes venom, comprises a catalytic subunit (VBC) and an inactive subunit (VAC).
- Retinal pigment epithelial (RPE) cells are crucial for retinal health and can be targets of toxins.
Purpose of the Study:
- To investigate the specific roles and interactions of vipoxin's subunits (VBC and VAC) in RPE cells.
- To elucidate the mechanisms underlying vipoxin-induced cellular responses, including cytotoxicity and genotoxicity.
- To determine how subunit interactions influence biological activity based on RPE cell characteristics.
Main Methods:
- Isolation and separation of vipoxin heterodimer into VBC and VAC subunits.
- Treatment of two RPE cell lines (RPE-1 and ARPE-19) with vipoxin and its subunits.
- Assessment of cell viability, cytotoxicity, cytoskeletal integrity, transepithelial resistance, apoptosis, and DNA damage.
- Analysis of p38 MAPK signaling pathway activation.
Main Results:
- Both VBC and VAC subunits induced cytotoxicity, cytoskeletal changes, apoptosis, and genotoxicity in RPE cells.
- VBC exhibited more pronounced catalytic and pharmacological effects in RPE-1 cells, causing significant DNA damage and cytotoxicity (up to 45%).
- VAC, while having minimal impact on membrane integrity, induced substantial DNA damage in ARPE-19 cells.
- Vipoxin's complex activities were modulated by subunit interactions and RPE cell microenvironment.
Conclusions:
- Vipoxin subunits (VBC and VAC) possess distinct and potent biological activities affecting RPE cell integrity and viability.
- Catalytic (VBC) and non-catalytic (VAC) mechanisms contribute to vipoxin's toxicity, with differential effects on RPE cell lines.
- Interactions between VBC and VAC are crucial for regulating vipoxin's complex biological functions, influenced by RPE cell-specific factors.
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