Importance of Snake Venom Metalloproteinases in Cell Biology: Effects on Platelets,Inflammatory and Endothelial Cells

Abstract

Snake venom metalloproteinases (SVMPs) are widely distributed in snake venoms and play important roles in hemostatic disorders and local tissue damage that follows snakebite. The impact of SVMPs on hemostasis has been extensively studied showing diverse effects both on soluble factors and cellular components. The action of SVMPs involves catalytic and anti-adhesive properties, as well as direct cellular activation and/or the release of endogenous bioactive components. The purpose of this review is to overview the action of SVMPs on the inhibition of platelet functions; angiogenesis, particularly inducing apoptosis of endothelial cells; and regarding the pro-inflammatory reaction that follows snakebite. We discuss the structural features of the molecules that may be involved in such activities. The versatility and availability of SVMPs make them important tools for cell biology research into the mechanisms of action of endogenous metalloproteinases, for insights into cellular-matrix interactions and for clinical investigations into the treatment of snakebites.

Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species

“…The hemorrhagic process triggered in the envenomation is directly related to the degradation of basement membrane, cell surface and plasma proteins due to catalytic properties of SVMPs [22,23]. Baldo and collaborators [57] demonstrated that a particular tissue accumulation of jararhagin in the basement membrane is essential for the damage of the blood vessels and suggested that this accumulation is due to the binding of the toxin to collagen.…”

“…Venom metalloproteinases, particularly PIII-SVMPs, are responsible for the local and systemic hemorrhage and are also involved in the local lesions due to their pro-inflammatory action or the ischemia at the site of the bite which arises from the reduction of blood supply following the damage of microvasculature [22,23]. Fortunately, PIII-SVMPs are highly immunogenic and are the predominant antigens recognized by commercial antivenoms for Bothrops snakes [20].…”

Matrix biology meets toxinology

“…However, not all proteolytically active enzymes are able to degrade the vascular matrix and act as hemorrhagins. Different domain structures of the PI-PIV SVMPs, different substrate specificities and other characteristics are controversially discussed to be the molecular landmarks of hemorrhagins which are responsible for the vessel-damaging activity (Escalante et al, 2006;Gutiérrez and Rucavado, 2000;Moura da Silva et al, 2007). Moreover, the concerted action of different venom components, their spatial and temporal distributions around the envenomation site and the dose-dependent, sometimes converse effects of venom components in the different tissues and organ environment will have to be discussed to explain the local tissue damage caused by venoms (recently reviewed by Gutiérrez et al, 2010).…”

“…Although the cleavage of laminins, nidogen and other basement membrane constituents can be recapitulated in vitro with the isolated components, the time course is much slower (Baramova et al, 1989;Escalante et al, 2006;Gutiérrez and Rucavado, 2000). Afterwards, additional venom activities synergistically destroy the integrity of the endothelial cell layer (Moura da Silva et al, 2007). Alternatively, endothelial cell-cell contacts, which are mainly mediated by VE-cadherin, are targeted by other venom proteinases (Ohsaka et al, 1975) or by proteolytic digestion products of fibrin (ogen) (Gröger et al, 2009;Petzelbauer et al, 2005).…”

Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study

“…These local effects have been defined as pain, hemorrhage, edema, myonecrosis and inflammation. The snake venom metalloproteinases (SVMPs) have been considered as playing a crucial role in the development of the local venom-induced pathogenesis (2)(3)(4).…”