Study of the degradome of HF3, a PIII-class snake venom metalloproteinase from Bothrops jararaca venom, on cultured fibroblasts

Abstract

Proteinases are the major components of viperid venom proteomes. In this context, snake venom metalloproteinases (SVMPs) are among the most abundant enzymes found in venoms and are responsible for several of the pathological effects of envenomation. The structural similarity of SVMPs with ADAMs (A Disintegrin and Metalloproteinase) and ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) has guided a number of functional assays currently employed in toxinology studies. The study of SVMPs activities in complex biological systems with the use of omics technologies has allowed the evaluation of several aspects of the pathology of the ophidian envenomation, as well as the signaling pathways triggered by SVMPs. Using complementary methodologies in proteomics and mass spectrometry the main goals of this project are to identify the alterations in the proteome of cultured fibroblasts subjected to the activity of HF3, a highly hemorrhagic P-III class SVMP isolated from Bothrops jararaca venom, as well as to evaluate in a high throughput fashion the substrate repertoire (degradome) of HF3 in cultured fibroblasts. The importance of this work is related to the use of a holistic approach for a better understanding of direct and indirect mechanisms of activity of HF3 upon cells. Moreover, the new findings will serve as a basis for the study of other metalloproteinases found in venoms or in the extracellular matrix of other vertebrates. (AU)