title: Insights into the local pathogenesis induced by fish toxins: role of natterins and nattectin in the disruption of cell-cell and cell-extracellular matrix interactions and modulation of cell migration.
abstract: Combined proteomic and transcriptomic approaches to study the composition of the venom of Thalassophryne nattereri venomous fish revealed the primary structures of the major toxins as a family of proteases natterins, never described on venoms and a C-type lectin nattectin. To gain new insights into the mechanisms of venom pathogenesis and to further elucidate the role of its major toxins, the natterins and nattectin, we undertook in vitro investigations using these isolated toxins. Here we demonstrated the specific ability of the nattectin to bind types I and V collagen and natterins to bind and cleave type I collagen as well as type IV collagen, disrupting cell attachment and HeLa cells survival. Natterins have cytotoxic effect on both adherent cells or at in suspension, showing direct induction of necrosis that is followed by cell detachment. Nattectin improves integrin-mediated HeLa cell adhesion and resistance to apoptosis by its binding to RGD-dependent integrins, especially the β1 subunit. Based on our studies we now report that extracellular matrix (ECM) components as well as the integrin β1 subunit are targets for the natterins and nattectin. The ECM degradation or remodeling activities exerted by these toxins affect cell-cell and cell-ECM adhesion and survival and impair inflammatory cell migration into inflamed tissues.
authors: Special Laboratory of Applied Toxinology, CEPID/FAPESP, Butantan Institute, Av Vital Brazil, 1500 Butantan, 05503 900 Sao Paulo, Brazil.
authors: Evilin Naname
authors: EN
authors: Komegae
authors: Anderson Daniel
authors: AD
authors: Ramos
authors: Ana Karina
authors: AK
authors: Oliveira
authors: Solange Maria de Toledo
authors: SM
authors: Serrano
authors: Mônica
authors: M
authors: Lopes-Ferreira
authors: Carla
authors: C
authors: Lima
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects*; D005397:Fish Venoms / Q000032:analysis / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors; D007610:Kallikreins / Q000633:toxicity*; D037181:Lectins, C-Type; D014118:Toxins, Biological / Q000633:toxicity*
chemical_list: D005397:Fish Venoms; D016023:Integrins; D037181:Lectins, C-Type; D014118:Toxins, Biological; D007610:Kallikreins