title: Effects of vipoxin and its components on HepG2 cells.
abstract: Snake venom Phospholipases A2 (svPLA2) are among the main toxic venom components with a great impact on different tissues and organs based on their catalytic specificity and a variety of pharmacological effects, whose mechanism is still under debate. The main toxic component, isolated from the venom of Vipera ammodytes meridionalis, is the heterodimeric postsynaptic ionic complex vipoxin, composed of a basic and toxic PLA2 enzyme subunit (GIIA secreted PLA2) and an acidic, enzymatically inactive and nontoxic subunit - vipoxin acidic component (VAC). This study demonstrates for the first time that vipoxin and its individual subunits affect integrity and viability of HepG2 cells displaying differences in their pharmacological activities. Under the experimental conditions, the individual PLA2 subunit induces cytotoxicity, cytoskeletal rearrangements and triggers early apoptosis in a concentration-dependent manner related to its enzymatic activity. Vipoxin and VAC do not affect cell viability but manifest high degree of genotoxicity, whereas DNA damage induced by PLA2 subunit could be defined as moderate and not associated with its catalytic activity. Our results suggest that the interactions between vipoxin subunits play an important role in HepG2 cell response and most likely affect the observed distinction between cyto- and genotoxicity.
authors.affiliation: Sofia University "St. Kliment Ohridski", Faculty of Biology, Department of Biochemistry, Sofia, Bulgaria.
authors.forename: Jordan
authors.initials: J
authors.lastname: Doumanov
authors.affiliation: Sofia University "St. Kliment Ohridski", Faculty of Biology, Department of Biochemistry, Sofia, Bulgaria.
authors.forename: Kirilka
authors.initials: K
authors.lastname: Mladenova
authors.affiliation: Sofia University "St. Kliment Ohridski", Faculty of Biology, Department of Cytology, Histology and Embryology, Sofia, Bulgaria.
authors.forename: Tanya
authors.initials: T
authors.lastname: Topouzova-Hristova
authors.affiliation: Bulgarian Academy of Sciences, Institute of Microbiology, Sofia, Bulgaria.
authors.forename: Stoyanka
authors.initials: S
authors.lastname: Stoitsova
authors.affiliation: Sofia University "St. Kliment Ohridski", Faculty of Biology, Department of Biochemistry, Sofia, Bulgaria. Electronic address: spetrova@biofac.uni-sofia.bg.
authors.forename: Svetla
authors.initials: S
authors.lastname: Petrova
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003599:Cytoskeleton / Q000187:drug effects; D004249:DNA Damage; D056945:Hep G2 Cells; D006801:Humans; D054467:Phospholipases A2 / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014757:Viper Venoms / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014757:Viper Venoms; C033134:vipoxin; D054467:Phospholipases A2
keywords: Apoptosis; Cytotoxicity; HepG2 cells; Vipoxin; sPLA(2)