title: Fibrinolytic and antiplatelet aggregation properties of a recombinant Cheonggukjang kinase.
abstract: This study characterized the efficacy of recombinant Cheonggukjang kinase (CGK) 3-5-rich fraction as a thrombolytic agent, which we overexpressed in Bacillus licheniformis ATCC10716, a strain normally lacking fibrinolytic activity. We found that CGK3-5 is a plasmin-like protease that directly degrades fibrin clots and does not activate plasminogen during fibrin clot lysis and platelet-rich clot lysis assays. We also confirmed antiplatelet and antithrombotic activity by CGK3-5-rich fraction both in vitro and in vivo. CGK3-5-rich fraction inhibited collagen-induced platelet aggregation in platelet-rich plasma in a concentration-dependent manner. The concentration of 1.5 mg/mL CGK3-5-rich fraction completely inhibited collagen-induced platelet aggregation. Furthermore, injection of CGK3-5-rich fraction into tail veins dose-dependently protected mice from death by pulmonary embolism induced by collagen and epinephrine. The survival rates were 30%, 70%, and 100%, respectively, with doses of 130 mg/kg, 260 mg/kg, and 520 mg/kg. These findings suggest that CGK3-5 holds promise as a treatment to mitigate the potentially effects of stroke and heart failure.
authors.affiliation: Department of Smart Foods and Drugs, Inje University, Gimhae, Gyeongnam, Korea.
authors.forename: Chinzorig
authors.initials: C
authors.lastname: Radnaabazar
authors.forename: Chung Mu
authors.initials: CM
authors.lastname: Park
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cha
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Song
mesh_terms: D000818:Animals; D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013025:Glycine max / Q000382:microbiology*; D013923:Thromboembolism / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D001426:Bacterial Proteins; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D011494:Protein Kinases