Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action

Abstract

Nowadays, proliferation of jellyfish has become a severe matter in many coastal areas around the world. Jellyfish Nemopilema nomurai is one of the most perilous organisms and leads to significant deleterious outcomes such as harm to the fishery, damage the coastal equipment, and moreover, its envenomation can be hazardous to the victims. Till now, the components of Nemopilema nomurai venom (NnV) are unknown owing to scant transcriptomics and genomic data. In the current research, we have explored a proteomic approach to identify NnV components and their interrelation with pathological effects caused by the jellyfish sting. Altogether, 150 proteins were identified, comprising toxins and other distinct proteins that are substantial in nematocyst genesis and nematocyte growth by employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF/MS). The identified toxins are phospholipase A2, phospholipase D Li Sic Tox beta IDI, a serine protease, putative Kunitz-type serine protease inhibitor, disintegrin and metalloproteinase, hemolysin, leukotoxin, three finger toxin MALT0044C, allergens, venom prothrombin activator trocarin D, tripeptide Gsp 9.1, and along with other toxin proteins. These toxins are relatively well characterized in the venoms of other poisonous species to induce pathogenesis, hemolysis, inflammation, proteolysis, blood coagulation, cytolysis, hemorrhagic activity, and type 1 hypersensitivity, suggesting that these toxins in NnV can also cause similar deleterious consequences. Our proteomic works indicate that NnV protein profile represents valuable source which leads to better understanding the clinical features of the jellyfish stings. As one of the largest jellyfish in the world, Nemopilema nomurai sting is considered to be harmful to humans due to its potent toxicity. The identification and functional characterization of its venom components have been poorly described and are beyond our knowledge. Here is the first report demonstrating the methodical overview of NnV proteomics research, providing significant information to understand the mechanism of NnV envenomation. Our proteomics findings can provide a platform for novel protein discovery and development of practical ways to deal with jellyfish stings on human beings.

Proteomic Analysis of the Venom of Jellyfishes Rhopilema esculentum and Sanderia malayensis

“…Other than metalloproteases, several serine proteases and serine carboxypeptidases were also identified in the venom proteomes. The presence of proteases has also been reported in the venom of several jellyfish species [ 24 , 25 , 26 , 31 , 33 ]. The functional role of proteases in jellyfish venom is not well understood; while based on observations in other venomous animals, we suggest that the proteases in the venom may be responsible for promoting the spreading and activation of other toxins [ 37 , 38 ].…”

“…Most of the toxins in this family share sequence similarity with ryncolins, a group of hemostasis-impairing toxins originally described from C. rynchops [ 21 ]. Ryncolin genes [ 22 ], transcripts, and proteins [ 23 , 24 , 25 , 26 ] have also been found in other species of jellyfish, but their functions are not well-characterized. C-type lectins, another major group of hemostasis-impairing toxins, are commonly found in the venoms of a wide variety of animals [ 27 , 28 , 29 , 30 ], including several jellyfish species: Pacific sea nettle Chrysaora fuscescens [ 31 ], Lion’s mane jellyfish Cyanea capillata, Nomura’s jellyfish N. nomurai [ 26 ], and cannonball jellyfish Stomolophus meleagris [ 23 ].…”

“…Mainly, they were homologous to zinc metalloproteinase-disintegrin-like and astacin-like metalloprotease, which were also identified in the proteome of the venom of other cnidarians, including Lion’s mane jellyfish C. capillata [ 26 ], sea wasp Chironex fleckeri [ 33 ], Pacific sea nettle C. fuscescens [ 31 ], ghost jellyfish Cyanea nozakii [ 34 ], Cyanea sp. [ 25 ], Nomura’s jellyfish N. nomurai [ 24 , 26 ], cannonball jellyfish S. Meleagris [ 23 ], and starlet sea anemone Nematostella vectensis [ 35 ]. It has been suggested that metalloprotease induces protease-mediated tissue damage by the degradation of the extracellular matrix, which eventually results in necrosis, edema, and hemorrhage [ 36 ].…”

“…Phospholipases, for example, were identified in the venom proteomes of both species, all of which were phospholipases A2 (PLA2s) with two and four copies of PLA2s in R. esculentum and S. malayensis venom, respectively. PLA2s has also been found in the venom of various other jellyfish species [ 23 , 24 , 25 , 26 , 31 , 33 , 34 , 39 , 40 ], and the PLA2 activity has been detected in the oral arm of R. esculentum [ 41 ]. PLA2s are considered hemolysin in jellyfish venom [ 42 ]; thus, we suspect that the presence of PLA2s in R. esculentum venom might be associated with its hemolytic activities reported previously [ 43 ].…”

Protective effect of epigallocatechin-3-gallate (EGCG) on toxic metalloproteinases-mediated skin damage induced by Scyphozoan jellyfish envenomation

“…Venom metalloproteinase is reported to play an important roles in the local pathogenesis, such as local myonecrosis, dermonecoris, and inflammatory reaction 39 , 40 . According to the analyses of transcriptome and proteome in schyphozoan jellyfish venom, metalloproteinase is one of the predominant components and largely contributes to the development of pathgenesis induced by the venom 41 – 45 . Snake venom metalloproteinases degrade extracellular matrix (ECM) that cause local hemorrhage and tissue damage 46 .…”