Activation of Bothrops jararaca snake venom gland and venom production: a proteomic approach.

Unlabelled: Viperidae venom glands have a basal-central lumen where the venom produced by secretory cells is stored. We have shown that the protein composition of venom gland changes during the venom production cycle. Here, we analyzed the venom gland proteins during the venom production cycle by proteomic approach. We identified specific proteins in each stage of the cycle. Protein species from endoplasmic reticulum (PDI and GPR78) and cytoplasm (actin, vimentin, tropomyosin, proteasome subunit alpha type-1, thioredoxin, and 40S ribosomal protein) are more abundant in the activated stage, probably increasing the synthesis and secretion of toxins. We also showed for the first time that many toxins are present in the secretory cells during the quiescent stage. C-type lectin-like and serine proteinases were more abundant in the quiescent stage, and GPIb-BP and coagulation factor IX/X were present only in this stage. Metalloproteinases, L-amino acid oxidases, PLA2 and snake venom metalloproteinase and PLA2 inhibitors, and disintegrins were more abundant in the activated stage. Regarding metalloproteinases, the presence of peptides corresponding to the pro-domain was observed. These results allow us to better understand the mechanism of venom gland activation and venom production, contributing to studies about snake toxins and their diversity.

Biological Significance: In this study we identified, for the first time, the presence of different toxins in the snake venom gland in its quiescent stage. Furthermore, we showed that not all toxins are synthesized during the activated stage of the gland, suggesting an asynchronous synthesis for different toxins. Besides, the synthesis of some protein species from endoplasmic reticulum and cytoplasm, which are related to the synthesis and secretion processes, are more abundant in the activated stage of this gland. The knowledge of the proteomic composition of the venom gland in different stages of the venom production cycle will give us new insights into the mechanism of venom gland activation and venom production, contributing to studies about snake toxins and their diversity.