Snake venoms promote stress-induced senescence in human fibroblasts
Anna Lewinska1, Aleksandra Bocian2, Vladimir Petrilla3,4
1Department of Cell Biochemistry, Faculty of Biotechnology, University of Rzeszow, Rzeszow, Poland.
Abstract:
Snake venoms are widely studied in terms of their systemic toxicity and proteolytic, hemotoxic, neurotoxic, and cytotoxic activities. However, little is known about snake-venom-mediated effects when used at low, noncytotoxic concentrations. In the current study, two human fibroblast cell lines of different origin, namely WI-38 fetal lung fibroblasts and BJ foreskin fibroblasts were used to investigate snake-venom-induced adaptive response at a relatively noncytotoxic concentration (0.01 µg/ml). The venoms of Indochinese spitting cobra ( Naja siamensis), western green mamba ( Dendroaspis viridis), forest cobra ( Naja melanoleuca), and southern copperhead ( Agkistrodon contortrix) were considered. Snake venoms promoted FOXO3a-mediated oxidative stress response and to a lesser extent DNA damage response, which lead to changes in cell cycle regulators both at messenger RNA and protein levels, limited cell proliferation and migration, and induced cellular senescence. Taken together, we have shown for the first time that selected snake venoms may also exert adverse effects when used at relatively noncytotoxic concentrations.
Insights
Snake venoms, even at low noncytotoxic concentrations, can trigger adaptive responses. These snake venom effects include oxidative stress, DNA damage, and cellular senescence, impacting cell proliferation and migration.
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Snake venoms are extensively researched for systemic toxicity and specific activities like proteolytic, hemotoxic, neurotoxic, and cytotoxic effects.
- Limited knowledge exists regarding snake venom's impact at low, noncytotoxic concentrations.
Purpose of the Study:
- To investigate the adaptive cellular responses induced by specific snake venoms at a noncytotoxic concentration.
- To explore the effects of Indochinese spitting cobra, western green mamba, forest cobra, and southern copperhead venoms on human fibroblast cell lines.
Main Methods:
- Utilized two human fibroblast cell lines: WI-38 fetal lung fibroblasts and BJ foreskin fibroblasts.
- Applied snake venoms at a low, noncytotoxic concentration (0.01 µg/ml).
- Analyzed FOXO3a-mediated oxidative stress and DNA damage responses, cell cycle regulators (mRNA and protein levels), cell proliferation, migration, and cellular senescence.
Main Results:
- Selected snake venoms induced a FOXO3a-mediated oxidative stress response.
- A lesser extent of DNA damage response was observed.
- Venoms limited cell proliferation and migration and induced cellular senescence.
- Changes in cell cycle regulators were noted at both mRNA and protein levels.
Conclusions:
- Demonstrated for the first time that certain snake venoms can exert adverse effects at relatively noncytotoxic concentrations.
- Highlights potential risks associated with low-dose exposure to specific snake venoms.
- Suggests a need for further research into the nuanced biological activities of snake venoms.
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