Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Snake venoms contain a rich variety of factors affecting the haemostatic mechanism which can be broadly classified as possessing coagulatant, anticoagulant and haemorrhagic activity. Coagulant enzymes include activators of blood coagulation factors II (prothrombin), V and X; anticoagulants include protein C activators, inhibitors of prothrombin complex formation and fibrinogenases which can be further classified according to their specificity for the alpha-, beta- and gamma-chains of fibrinogen. Intermediate between true coagulants and true anticoagulants are the thrombin-like enzymes which bring about clotting in vitro but defibrination (anticoagulation) in vivo. Snake venoms also affect platelets either by inducing or inhibiting platelet aggregation and cause haemorrhage via an action on platelets or via proteolysis of the blood vessel wall. Haemorrhagins also include inter alia, the alpha-fibrinogenases. This rich diversity of snake venom components affecting haemostasis has enabled a range of practical applications to be established including therapeutic anticogulation with thrombin-like enzymes (Ancrod and Defibrase) and laboratory tests for individual haemostatic factors (protein C, prothrombin, factor X and lupus anticoagulant). This broad spectrum of materials in snake venoms suggests some evolutionary advantage to the venom producer, not only for dispatching prey but as agents which 'spread' the venom toxins throughout the body and initiate digestion.
 ...
PMID:Snake venoms affecting the haemostatic mechanism--a consideration of their mechanisms, practical applications and biological significance. 807 11

Reptilase, defibrase and ancrod are thrombin-like venom enzymes that cleave fibrinogen to release fibrinopeptide-A and generate fibrin monomers. Although these enzymes decrease fibrinogen levels in vivo, presumably by enhancing fibrinolytic activity, the mechanism has not been identified. In the present study, we analyzed their effects on the inhibitors of fibrinolysis. Plasminogen activator inhibitor-1 (PAI-1) was cleaved at its C-terminus by reptilase and lost its specific activity. Alpha2-antiplasmin (alpha2-AP) was cleaved both at the Pro19-Leu20 peptide bond and at its C-terminus by reptilase, and also lost its specific activity. The apparent second-order rate constants (mol/l per min per Batroxobin unit) were 0.22 for the cleavage of PAI-1 (3.2 micromol/l) and 0.19 for that of alpha2AP (6.4 micromol/l), which were approximately 200-fold lower than that (47.0) for the cleavage of fibrinogen (1.1 micromol/l). Neither defibrase nor ancrod cleaved and inactivated these inhibitors. Only reptilase enhanced euglobulin clot lysis in vitro at high concentration, due probably to PAI-1 inactivation. Since all these three enzymes enhance fibrinolysis similarly during defibrination therapy, the neutralization or inactivation of the inhibitors of fibrinolysis appeared not to represent the main mechanism for the enhancement.
 ...
PMID:The cleavage and inactivation of plasminogen activator inhibitor type 1 and alpha2-antiplasmin by reptilase, a thrombin-like venom enzyme. 1075 7

Batroxobin, the thrombin-like enzyme, is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied the neuroprotective effect of batroxobin on anoxic hippocampal neurons in vitro. The purpose of this study was to obtain further information on the mechanism of the batroxobin-induced neuroprotection and examine the neuroprotective effect on neurons exposed to anoxia. The effect of batroxobin on anoxic damages in cultured hippocampal neurons of neonatal rats was investigated by using morphological changes and heat shock protein 70 Kd (Hsp70) immunoreactive expression as indicators. The results indicate that batroxobin, besides its defibrination, may have a direct neuroprotective effect on anoxic damage of hippocampal neurons.
 ...
PMID:Batroxobin against anoxic damage of rat hippocampal neurons in culture: morphological changes and Hsp70 expression. 1178 32