Purification and some properties of autoprothrombin II-A: An anticoagulant perhaps also related to fibrinolysis
1972; Elsevier BV; Volume: 1; Issue: 5 Linguagem: Inglês
10.1016/0049-3848(72)90052-7
ISSN1879-2472
AutoresWalter H. Seegers, Lowell E. McCoy, Hans D. Groben, N Sakuragawa, B.B.L. Agrawal,
Tópico(s)Hemophilia Treatment and Research
ResumoMethods were developed for the assay and isolation of autoprothrombin II-A. The purified protein retarded blood coagulation in vitro as well as in vivo and induced fibrinolysis. It is tentatively concluded that the protein originated from prothrombin and possessed inhibitor-activator qualities respectively as anticoagulant and fibrinolytic agent. To obtain Auto II-A, concentrated prothrombin complex was digested with purified thrombin. Chromatography on a DEAE-cellulose column separated prethrombin, Auto II-A, and autoprothrombin III (Factor X). The inhibitor-activator was then purified by using a Sephadex G-100 or G-100 superfine column. A single component was indicated by polyacrylamide gel electrophoresis and by ultracentrifugation. The equation for S20,w0 was 3.9 + 0.0114X. Isoelectric point = pH 3.9. It is a competitive inhibitor of autoprothrombin C (Factor Xa). N-terminal amino acids were Ile and Gly. An amino acid analysis was compared with a new amino acid analysis of purified prothrombin. The latter had 518 amino acid residues per mole. The protein contained sialic acid, neutral sugars, and amino sugars. Serum from rabbits immunized with purified prothrombin crossreacted with purified Auto II-A. A working theory is proposed as follows: Thrombin functions in a negative feedback system which retards thrombin formation due to the production of prethrombin and Auto II-A. Platelet factor 3 also produced prethrombin and Auto II-A. This feedback system could be the molecular basis of latent coagulation and fibrinolysis. In accelerated coagulation, the latent coagulation sequences are by-passed with massive formation of fibrin.
Referência(s)