An overview of the immune modulating effects of enzymatic toxins from snake venoms.

Snake venoms are complex mixtures of organic and inorganic compounds, including proteins belonging to the protease (serine and metalloproteinases), oxidase (L-amino acid oxidases), and phospholipase (especially phospholipases A2) enzyme classes. These toxins account for the serious deleterious effects of snake envenomations, such as tissue necrosis, neurotoxicity, and hemorrhage. In addition to their toxic effects, snake venom toxins have served as important tools for investigating the mechanisms underlying envenomation and discovering new pharmacologically active compounds with immunotherapeutic potential. In this sense, the present review discusses the new findings and therapeutic perspectives in the immune modulating potential of enzymatic toxins from snake venoms belonging to the classes metalloproteinase, serine protease, L-amino acid oxidase, and phospholipase A2.

Functional Elucidation of Nemopilema nomurai and Cyanea nozakii Nematocyst Venoms' Lytic Activity Using Mass Spectrometry and Zymography.

BACKGROUND: Medusozoans utilize explosively discharging penetrant nematocysts to inject venom into prey. These venoms are composed of highly complex proteins and peptides with extensive bioactivities, as observed in vitro. Diverse enzymatic toxins have been putatively identified in the venom of jellyfish, Nemopilema nomurai and Cyanea nozakii, through examination of their proteomes and transcriptomes. However, functional examination of putative enzymatic components identified in proteomic approaches to elucidate potential bioactivities is critically needed. METHODS: In this study, enzymatic toxins were functionally identified using a combined approach consisting of in gel zymography and liquid chromatography tandem mass spectrometry (LC-MS/MS). The potential roles of metalloproteinases and lipases in hemolytic activity were explored using specific inhibitors. RESULTS: Zymography indicated that nematocyst venom possessed protease-, lipase- and hyaluronidase-class activities. Further, proteomic approaches using LC-MS/MS indicated sequence homology of proteolytic bands observed in zymography to extant zinc metalloproteinase-disintegrins and astacin metalloproteinases. Moreover, pre-incubation of the metalloproteinase inhibitor batimastat with N. nomurai nematocyst venom resulted in an approximate 62% reduction of hemolysis compared to venom exposed sheep erythrocytes, suggesting that metalloproteinases contribute to hemolytic activity. Additionally, species within the molecular mass range of 14-18 kDa exhibited both egg yolk and erythrocyte lytic activities in gel overlay assays. CONCLUSION: For the first time, our findings demonstrate the contribution of jellyfish venom metalloproteinase and suggest the involvement of lipase species to hemolytic activity. Investigations of this relationship will facilitate a better understanding of the constituents and toxicity of jellyfish venom.

Biochemical and kinetic evaluation of the enzymatic toxins from two stinging scyphozoans Nemopilema nomurai and Cyanea nozakii.

Jellyfish envenomations are emerging as an important public health concern occurred worldwide. In China, the situation is getting worse with numerous people stung by jellyfish Nemopilema nomurai (N. nomurai) and Cyanea nozakii (C. nozakii) in the summer. However, the proteinaceous mixtures in nematocysts responsible for the symptoms of jellyfish stings were scarcely characterized and understood in view of enzymatic constituents and toxicity. In the present study, enzymatic properties of jellyfish N. nomurai and C. nozakii nematocyst venom were analyzed biochemically and kinetically. The current data revealed that N. nomurai and C. nozakii nematocyst venom exhibited various enzymatic activities, of which metalloproteinases activity and PLA2s-like activity were predominant. Moreover, the catalytic activities of metalloproteinases and PLA2s-like were dependent on different physiochemical conditions such as temperature, pH and divalent ions. Kinetic profiling revealed their catalytic behaviors fitted the Michaelis-Menten equation under specific conditions. Findings suggested jellyfish nematocyst venom possessed diverse enzymatic constituents, which may underlie the extensively characterized bioactivities of jellyfish venom and human envenomations. Hence, our study will contribute to understanding the enzymatic constituents and toxicity of jellyfish nematocyst venom and may afford potential therapeutic targets for developing drugs for jellyfish stings.