Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease.

摘要: Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 envenomations and 100,000 deaths each year. envenomation also causes innumerable morbidities, specifically loss of limbs as result excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are predominant component viper venoms, involved the degradation basement membrane proteins (particularly collagen) surrounding tissues bite site. Although their collagenolytic properties have been established, molecular mechanisms through which SVMPs induce permanent muscle damage poorly understood. Here, we demonstrate purification characterisation an SVMP from (Crotalus atrox) venom. Mass spectrometry analysis confirmed this protein most likely to be group III metalloprotease (showing high similarity VAP2A) has referred CAMP atrox metalloprotease). displays both fibrinogenolytic activities inhibits CRP-XL-induced platelet aggregation. To determine its effects on damage, was administered into tibialis anterior mice actions were compared with cardiotoxin I (a three-finger toxin) elapid snake (Naja pallida) Extensive immunohistochemistry analyses revealed significantly damages skeletal muscles by attacking collagen scaffold other important proteins, prevents regeneration disrupting functions satellite cells. In contrast, destroys damaging plasma membrane, but does not impact due inability affect extracellular matrix. Overall, study provides novel insights