Zinc Metalloproteinase-Disintegrin Jararhagin (JF I) Bothrops Jararaca Recombinant Protein

Snake venom zinc metalloproteinase-disintegrin-like jararhagin: causes hemorrhage. This is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. It is able to degrade von Willebrand factor (vWF) and it hydrolyzes the alpha-chain of fibrinogen (FGA) while leaving the beta and gamma chains unaffected. It inhibits collagen-induced platelet aggregation through the binding to alpha-2/beta-1 integrin (ITGA2/ITGB1) (collagen receptor), and it cleaves the beta-1 subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. It has inability to be affected by the plasma inhibitor alpha2-macroglobulin. In fibroblasts, it functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. It induces a strong pro-inflammatory response characterized by intense leukocyte accumulation and release of cytokines at the site of the injection. Although hemorrhage and edema are a response to the direct effect of this toxin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. It also possesses anti-tumorgenic properties.