A peptide derivative (1-70 fragment) of protein SV-IV accelerates human blood coagulation in vitro by selective inhibition of the heparin-induced antithrombin III activation process.
The effect of two peptide derivatives of the rat SV-IV (SV-IV/A: 1-70 fragment; SV-IV/B: 71-90 fragment) on human blood coagulation was investigated. The SV-IV/A fragment was found to possess the same procoagulant activity of the native protein, whereas SV-IV/B retained only a very small fraction of the activity. The results obtained strongly suggest that the procoagulant activity of SV-IV/A is due, like SV-IV, to a selective inhibition of the antithrombin III (AT III) activation process induced by heparin, an essential cofactor of AT III. The main data supporting this hypothesis are the following: 1) the concentration of active serum AT III decreases when SV-IV/A is present in the clotting system; 2) the plasma treatment with SV-IV/A reduces the concentration of AT III, but not that of other plasma serine protease inhibitors; 3) the recalcification time (RT) of the plasma treated with a rabbit anti-AT III polyclonal antiserum is not modified by SV-IV/A; 4) the presence of SV-IV/A in a reaction mixture containing pure fibrinogen, alpha-thrombin, heparin, and AT III neutralizes the thrombin inhibition induced by AT III; 5) the concentration of the thrombin-AT III complexes, occurring in sera obtained from CaCl2-coagulated plasma, is markedly reduced in the presence of SV-IV/A; 6) appropriate concentrations of heparin neutralize the inhibitory effect of either SV-IV/A or SV-IV on the AT III activity in vitro.
Di Micco
B
B
Department of Biochemistry and Biophysics, II University of Naples, Italy.
Stiuso
P
P
Colonna
G
G
Porta
R
R
Marchese
M
M
Schinina
M E
ME
Macalello
M A
MA
Metafora
S
S
D000818:Animals; D000990:Antithrombin III / Q000037:antagonists & inhibitors*; D001324:Autoantigens / Q000737:chemistry*; D001777:Blood Coagulation / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D029607:Seminal Vesicle Secretory Proteins
D001324:Autoantigens; D010446:Peptide Fragments; D029607:Seminal Vesicle Secretory Proteins; C085073:seminal vesicle autoantigen; D000990:Antithrombin III; D006493:Heparin