title: A bi-functional anti-thrombosis protein containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities.
abstract: Direct-acting fibrin(ogen)olytic agents such as plasmin have been proved to contain effective and safety thrombolytic potential. Unfortunately, plasmin is ineffective when administered by the intravenous route because it was neutralized by plasma antiplasmin. Direct-acting fibrin(ogen)olytic agents with resistance against antiplasmin will brighten the prospect of anti-thrombosis. As reported in 'Compendium of Materia Medica', the insect of Eupolyphaga sinensis Walker has been used as traditional anti-thrombosis medicine without bleeding risk for several hundreds years. Currently, we have identified a fibrin(ogen)olytic protein (Eupolytin1) containing both fibrin(ogen)olytic and plasminogen-activating (PA) activities from the beetle, E. sinensis.
  
  
  OBJECTIVE
  To investigate the role of native and recombinant eupolytin1 in fibrin(ogen)olytic and plasminogen-activating processes.
  
  
  RESULTS
  Using thrombus animal model, eupolytin1 was proved to contain strong and rapid thrombolytic ability and safety in vivo, which are better than that of urokinase. Most importantly, no bleeding complications were appeared even the intravenous dose up to 0.12 µmol/kg body weight (3 times of tested dose which could completely lyse experimental thrombi) in rabbits. It is the first report of thrombolytic agents containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities.
  
  
  CONCLUSIONS
  The study identified novel thrombolytic agent with prospecting clinical potential because of its bi-functional merits containing both plasmin- and PA-like activities and unique pharmacological kinetics in vivo.
authors.affiliation: Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Yang
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Cunbao
authors.initials: C
authors.lastname: Liu
authors.forename: Huahu
authors.initials: H
authors.lastname: Ye
authors.forename: Fengliang
authors.initials: F
authors.lastname: Li
authors.forename: Haining
authors.initials: H
authors.lastname: Yu
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058833:Antithrombin Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D001760:Bleeding Time; D001517:Coleoptera; D005342:Fibrinolysis / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D010960:Plasminogen Activators / Q000378:metabolism*; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
chemical_list: D058833:Antithrombin Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator