Snake venoms promote stress‐induced senescence in human fibroblasts

Abstract

Snake venoms are widely studied in terms of their systemic toxicity and proteolytic, hemotoxic, neurotoxic, and cytotoxic activities. However, little is known about snakevenom-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-venominduced 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. K E Y W O R D Scellular senescence, fibroblasts, oxidative stress and DNA damage response (DDR), proliferation, snake venoms

Evaluation of Antifungal Activity of Naja pallida and Naja mossambica Venoms against Three Candida Species

“…The venom composition of both analyzed species is very similar and typical for the Naja genus with the abundance of 3FTx proteins [13][14][15][16]. In contrast, we observed a relatively lower content of PLA 2 ( Figure 1) compared to other cobra species that may be due to a different methodological approach used for protein quantification [17] and age-, sex-or season-related effects on venom composition [7,18].…”

Venomics and Cellular Toxicity of Thai Pit Vipers (Trimeresurus macrops and T. hageni)

“…However, the latter exhibited a greater sensitivity to both Trimeresurus venoms, indicating a greater abundance of molecular targets for proteolytic enzymes. In addition, Foxo-3-mediated oxidative stress DNA damage leading to cellular senescence was recently reported in fibroblasts exposed to non-lethal doses of Naja siamensis, Naja melanoleuca, and Dendroaspis viridis venoms [47]. Such effects could also be stimulated by pit viper venoms.…”

Comparison of Methods for Measuring Protein Concentration in Venom Samples

“…In the 2-D Quant Kit method, copper ions attach to the peptide bonds in the protein, so this method is independent of the amino acid composition of the proteins in the sample. This kit has been repeatedly used to measure the concentration of proteins in venom [28,39] and this is also the most commonly used method in our laboratory [10,34,35,40]. However, obtained results by 2-D Quant Kit and Bradford for A. contortrix venom show low variability, whereas for N. ashei venom, the differences are large.…”

“…However, obtained results by 2-D Quant Kit and Bradford for A. contortrix venom show low variability, whereas for N. ashei venom, the differences are large. This observation could explain why we have never managed to obtain well-separated and optimized gels for species of the genus Naja [40] and Dendroaspis, and we have had no problems with Viperids [10,34]. As the gel staining procedure involves the use of Coomassie Brillant Blue, which is also the dye in the Bradford method, the significant difference in the concentration values obtained from Bradford and 2-D Quant kit assays in the case of Naja ashei may be the reason why we observed gels that were not stained enough as if we added too few proteins.…”