Proteolytic enzymes from snake venoms trigger cascades of yet unknown molecular events

Abstract

The proteinase domain of hemorrhagic snake venom metalloproteinases (SVMPs) is believed to function to degrade capillary basement membranes, endothelial cell surfaces, and stromal matrix ultimately causing extravasation of capillary contents into the surrounding stroma. Hemorrhagic factor 3 (HF3) is a glycosylated P-III SVMP isolated from Bothrops jararaca venom. HF3 is an extremely active toxin that shows a minimum hemorrhagic dose of 240 fmol on the rabbit skin. Previous studies have shown that HF3 degrades plasma and extracellular matrix proteins such as fibronectin, vitronectin, fibrinogen, von Willebrand factor, and collagens IV and VI. Analysis of HF3 effects on the mice dermis analyzed by proteomic approaches revealed a decrease of proteins related to cytoskeleton and extracellular matrix. The aims of this project are to improve the in vivo molecular characterization of the effects of HF3 and to characterize the hemorrhagic tissue regeneration. To tackle the challenge of uncovering putative molecular cascades triggered by HF3 we have adopted a systemic approach by proteomics based on mass spectrometry. (AU)