Snake Venom Hemotoxic Enzymes: Biochemical Comparison between Crotalus Species from Central Mexico

Abstract

Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

“…Contrary to our results, Soto et al [88] described that C. scutulatus venom lacks gelatinolytic activity. Also, a study performed by Roldán-Padrón et al [89] demonstrated that the venom caseinolytic activity of C. atrox is higher than that of C. m. nigrescens.…”

A Meta-Analysis of the Protein Components in Rattlesnake Venom

“…This synergism causes the joint effects of multiple toxins to assert greater effects than the sum of individual potencies [ 73 ], making trace amount of snake venom to be highly efficient and effective [ 73 , 74 ]. Such combinations of venom proteins often cause various symptoms of bleedings, tissue degradation, necrosis, and further complications in prey and bite victims [ 69 , 177 ] and improve the lethality of whole crude venom in contrast to individual components [ 73 , 178 ].…”

“…Rattlesnakes possess various different toxins from 10–20 protein families [ 7 , 30 , 40 , 41 , 42 ]. These families possess several enzymes, such as: L-amino acid oxidases (LAAO) [ 30 , 43 , 44 , 45 , 46 ], phosphodiesterase (PDE) [ 47 , 48 , 49 ], snake venom metalloproteases (SVMP) [ 50 , 51 , 52 ], serine proteases (SVSP) [ 44 , 53 , 54 , 55 ], phospholipases (PLA 2 ) [ 56 , 57 , 58 , 59 ].Additionally, rattlesnake venoms also contain nonenzymatic proteins like myotoxin a and its homologs [ 60 , 61 , 62 , 63 ], bradykinin-potentiating peptides and bradykinin-inhibitory peptide (BPPs and BIPs) [ 30 , 44 , 64 , 65 ], disintegrins (Dis) [ 3 , 44 , 45 , 55 , 66 , 67 , 68 ], cysteine-rich secretory proteins (CRiSPs) [ 2 , 45 , 55 , 62 ], and C-type lectins (CTL) [ 30 , 41 , 48 , 69 ]. It is not uncommon to have variation in venom composition within species [ 17 , 23 ].…”

“…A natural solution to this issue is quantifying the relationship between venom components rather than individual units. For example, within Crotalus polystictus , the type and potency of proteins expressed vary with age and sex [ 48 , 69 , 70 , 71 ]. Many venom components discovered, such as LAAO and PDE, have not been explored for their potential biomedical applications [ 32 , 72 ].…”

Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving

“…SVSPs are well-studied venom enzymes affecting generally the hemostatic system. Individually, they are not considered lethal, but they contribute to the toxic effect when combined with other proteins of the venom [39,40]. Fundamentally, SVSPs can be categorized into different subtypes depending on their mode of action to include thrombin-like enzymes, kallikrein-like, plasminogen activators, platelet aggregation inhibitors, protein-C activators and prothrombin activators [41].…”