Alpha-type phospholipase A2 inhibitors from snake blood

Abstract

It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA2 toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA2s. The present study aimed to review the currently available literature on PLA2 and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A2 and myotoxins, complementing the conventional serum therapy.

Venom Profiling of the Insular Species Bothrops alcatraz: Characterization of Proteome, Glycoproteome, and N-Terminome Using Terminal Amine Isotopic Labeling of Substrates

“…66,67 Moreover, PLA2 inhibitors found in snake blood contain a region with high similarity to the carbohydrate recognition domain of C-type lectins. 68,69 Thus, our results suggest that the interaction between PLA2 and lectins could be specific; however, further experiments would be necessary to confirm this finding.…”

“…The application of lectin-affinity chromatography for glycoproteome profiling is not a straightforward approach, and, in the case of Bothrops venoms, it may result in the binding of nonglycosylated proteins to the resin due to a possible unspecific interaction mediated by lectin regions outside the carbohydrate recognition domain . Nevertheless, in the case of PLA2s, previous studies showed the interaction of lectins and members of this toxin class. − Interestingly, mammalian-secreted PLA2s are also recognized by receptors that contain C-type lectin domains. , Moreover, PLA2 inhibitors found in snake blood contain a region with high similarity to the carbohydrate recognition domain of C-type lectins. , Thus, our results suggest that the interaction between PLA2 and lectins could be specific; however, further experiments would be necessary to confirm this finding.…”

A Comprehensive Multi-Omic Approach Reveals a Relatively Simple Venom in a Diet Generalist, the Northern Short-Tailed Shrew, Blarina brevicauda

“…Many venomous snakes are known to have inhibitory proteins in their circulatory systems that can act as direct antagonists to their own venom components ( Mackessey 2010 ; Santos-Filho and Santos 2017 ). It is possible that the double-headed protease inhibitor found in B. brevicauda ’s submaxillary gland serves a similar function.…”

Venom proteomic analysis of medically important Nigerian viper Echis ocellatus and Bitis arietans snake species

“…Available literature reports that the blood plasma of numerous snake species are naturally composed of endogenous phospholipase A 2 inhibitors, generally known as snake blood phospholipase A 2 inhibitors (sbPLIs). Primarily, they neutralize deleterious effects of phospholipase A 2 [ 82 , 83 ]. It implies that sbPLIs exert self-protection role against the enzymes of their own venom, which eventually reach the circulatory system [ 82 , 83 ].…”

“…Primarily, they neutralize deleterious effects of phospholipase A 2 [ 82 , 83 ]. It implies that sbPLIs exert self-protection role against the enzymes of their own venom, which eventually reach the circulatory system [ 82 , 83 ]. What seems new is the fact that phospholipase A 2 inhibitory protein was detected in the venom, revealing that the protein is not only expressed in the snake blood serum.…”