OXIDATIVE MODIFICATION OF FIBRINOGEN INHIBITS THROMBIN-CATALYZED CLOT FORMATION

被引:110
作者
SHACTER, E
WILLIAMS, JA
LEVINE, RL
机构
[1] NCI,GENET LAB,BETHESDA,MD 20892
[2] NHLBI,BIOCHEM LAB,BETHESDA,MD 20892
基金
美国国家卫生研究院;
关键词
PROTEIN OXIDATION; FIBRINOGEN; CLOTTING; DYSFIBRINOGENEMIA; FREE RADICALS;
D O I
10.1016/0891-5849(95)93872-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Plasma fibrinogen plays a central role in controlling hemostasis. In an earlier report, we found that fibrinogen is oxidized when whole plasma is treated with a metal-catalyzed oxidation system. These studies show that oxidative modification of purified human fibrinogen leads to an exposure-dependent loss of thrombin-induced clot formation. Inhibition of clotting occurred when either metal-catalyzed oxidation or gamma-irradiation was employed to generate oxidizing radicals. Both systems caused covalent modification of fibrinogen, assessed by measuring incorporation of protein carbonyls. Thrombin-catalyzed fibrinopeptide release was normal in irradiated fibrinogen and was only slightly diminished in protein exposed to metal-catalyzed oxidation, indicating that the inhibition of clotting activity was due to impaired fibrin monomer polymerization. Thus, oxidative modification of normal fibrinogen causes dysfibrinogenemia and constitutes a novel mechanism for inhibition of thrombosis.
引用
收藏
页码:815 / 821
页数:7
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