抄録
One of the serine protease inhibitors, Antithrombin III (AT III) plays an important roles on the development of hypercoagulable state and this experimental studies were designed to investigate its metabolic kinetics from aspect of AT III biosynthesis in rat.
AT III was purified by heparin Sepharose affinity chromatography and as a precursor of AT III 14C-Glycine was utilized. From the radioactivity into AT III fractions of rat tissues, its biosynthesis was evaluated on the effect of some experimental conditions.
In order to investigate the effect of the ischemia in liver on AT III synthesis, one lobe of liver was ligated for 2 or 4 hours after intraportal injection of 14C-Glycine, and compared with non-ligated liver lobes. The biosynthesis of AT III was inhibited 64% for 2 hour-ligated liver lobe and 79% for 4 hour-ligated one, while the biosynthesis of tissue proteins was inhibited 56% for 4 hour-ligated liver lobe but there was no difference for 2 hour-ligated one.
Intraperitonially injected Ethionine, ATP depleting agent, inhibited the incorporation of 14C-Glycine into both AT III fractions and tissue proteins but the biosynthesis of AT III was more remarkably inhibited than tissue proteins in liver. The ratio of 14C-Glycine incorporation into AT III/tissue proteins was reduced in liver (p<0.01).
It can be said that ischemia and/or ATP depletion in liver inhibit the biosynthesis of AT III more prominently than other tissue proteins.
These results suggest a possibility of vicious cycle between the inhibition of AT III biosynthesis in ATP depletion induced by ischemia and the development of hypercoagulable state due to circulating disorders.
