Antiplatelet and antithrombotic activity of a fibrin(ogen)olytic protease from Bacillus cereus strain FF01.
Fibrin(ogen)olytic enzymes offer great promise for the treatment of thrombosis associated disorders. The present study describes the characterization of an extracellular fibrin(ogen)olytic serine protease (named Bacethrombase) purified from the Bacillus cereus strain FF01. The molecular mass of the Bacethrombase was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and matrix assisted laser desorption/ionization-time-of-flight-mass spectroscopy analyses at 39.5 kDa and 38,450.51 Da, respectively. The peptide mass fingerprinting and analyses of the composition of the amino acids revealed the similarity of the Bacethrombase to the bacterial serine proteases. The secondary structure of the Bacethrombase was composed of 14% helix, 6.6% beta-sheet, and 79.4% random coil. Bacethrombase was found to contain 48% sialic acid and it preferentially degraded the Aα-chain of fibrinogen, as well as fibrin. The anticoagulant potency of the Bacethrombase was comparable with that of warfarin and heparin, and was corroborated by its fibrinogenolytic activity rather than the inhibition of thrombin, prothrombin or FXa. Bacethrombase demonstrated antiplatelet activity, and dose-dependently inhibited the ADP-induced platelet aggregation. Bacethrombase (10 mg/kg) did not show toxicity after i.v. administration in Wistar rats; however, it revealed an in vivo anticoagulant effect and significantly inhibited the carrageenan-induced in vivo thrombus formation in rats.
['Majumdar|Sourav|S|', 'Dutta|Sumita|S|', 'Das|Tanusree|T|', 'Chattopadhyay|Pronobesh|P|', 'Mukherjee|Ashis K|AK|']
D000818:Animals D000991:Antithrombins D001409:Bacillus cereus D001426:Bacterial Proteins D015951:Factor Xa D005343:Fibrinolytic Agents D006031:Glycosylation D006801:Humans D010974:Platelet Aggregation D010975:Platelet Aggregation Inhibitors D011499:Protein Processing, Post-Translational D017433:Protein Structure, Secondary D059748:Proteolysis D017208:Rats, Wistar D020539:Sequence Analysis, Protein D013379:Substrate Specificity D013917:Thrombin
Antiplatelet Anticoagulant Thrombolytic agent