Kinetic studies on the effect of heparin and fibrin on plasminogen activators.
نویسنده
چکیده
1. Possible interactions between fibrin(ogen) and heparin in the control of plasminogen activation were studied in model systems using the thrombolytic agents tissue-type plasminogen activator (t-PA), urokinase and streptokinase.plasminogen activator complex and the substrates Glu- and Lys-plasminogen. 2. Both t-PA and urokinase activities were promoted by heparin and by pentosan polysulphate, but not by chondroitin sulphate or hyaluronic acid. The effect was on Km. 3. In the presence of soluble fibrin (and its mimic, CNBr-digested fibrinogen) the effect of heparin on t-PA was attenuated, although not abolished. In studies using a monoclonal antibody and 6-aminohexanoic acid, it was found that heparin and fibrin did not seem to share a binding site on t-PA. 4. The activity of t-PA B-chain was unaffected by heparin, so the binding site is located on the A-chain of t-PA (and urokinase). 5. Fibrin potentiated the activity of heparin on urokinase. The activity of streptokinase.plasminogen was unaffected by heparin whether or not fibrin was present. 6. If these influences of heparin and fibrin also occur in vivo, then, in the presence of heparin, the relative fibrin enhancement of t-PA will be diminished and the likelihood of systemic activation by t-PA is increased.
منابع مشابه
اثر آنتی بادی های منوکلونال ضد پلاسمینوژن انسانی بر فعال شدن گلو-پلاسمینوژن انسانی بوسیله فعال کننده های پلاسمینوژن
Background: Human plasminogen is a plasma glycoprotein synthesized mainly in the liver. Conversion of plasminogen to plasmin by plasminogen activators is a key event in the fibrinolytic system. In this study, we investigated the effects of two anti-human plasminogen monoclonal antibodies, A1D12 and MC2B8 on Glu-plasminogen activation in presence of u-PA, t-PA and streptokinase. Methods: Produci...
متن کاملپتانسیل آنتی‌پلاسمینوژن منوکلونال آنتی‌بادی در دستکاری دو سیستم فیبرینولیز و آنژیوژنز
Background: Plasminogen has a central role in fibrinolyrtic system can activate through various activators (PAs) to its active form plasmin and perfoem its vital function that is fibrin clot lysis. Furthermore the fibrinolyrtic system plays a major role in angiogenesis. The fibrinolyrtic system activation control cell migration and invasion. In addition to this, plasmin regulates tumor growth. ...
متن کاملKinetic studies on novel plasminogen activators
The activation of plasminogen by two novel hybrid enzymes, constructed from the A-chain of plasmin and the B-chains of tissue-type plasminogen activator (t-PA) or urokinase, was compared with the activation by the parent enzymes. Basal kinetic constants for 'Lys-plasminogen' (human plasminogen with N-terminal lysine) and 'Glu-plasminogen' (human plasminogen with N-terminal glutamic acid) activa...
متن کاملThe interaction of streptokinase - plasminogen activator complex , tissue - type plasminogen activator , urokinase and their acylated derivatives with fibrin and cyanogen bromide digest of fibrinogen
The effects of purified soluble fibrin and of fibrinogen fragments (fibrin mimic) on the activation of Lysplasminogen (i.e. plasminogen residues 77-790) to plasmin by streptokinase plasminogen activator complex and by tissue-type plasminogen activator were studied. Dissociation constants of both activators were estimated to lie in the range 90-160 nm (fibrin) and 16-60 nM (CNBr-cleavage fragmen...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Biochemical journal
دوره 249 1 شماره
صفحات -
تاریخ انتشار 1988