Purification and partial characterization of plasminogen activator from human uterine tissue

Rijken, D.C.; Wijngaards, G.; Jong, M. Zaal-de; Welbergen, J.

doi:10.1016/0005-2795(79)90205-8

Cited by 317 publications

(165 citation statements)

References 23 publications

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“…The t-PA preparations isolated from uterus [5], heart [7] and melanoma cells [4] in the absence of aprotinin are principally in the two-chain form.…”

Section: Discussionmentioning

confidence: 99%

“…The incorporation of diisopropylfluorophosphate into an active form of t-PA [4,5] and the primary structure of t-PA predicted from its c-DNA sequence [6] revealed that this protein is a typical serine protease. t-PA isolated from tissues [5,7] or cell culture [4] is an active enzyme that is Abbreviations: t-PA, tissue plasminogen activator; -p-NA, -p-nitro-anilide; SBTI, soybean trypsin inhibitor; LBTI, lima bean trypsin inhibitor; HMW-kininogen, high molecular mass kininogen; TBS, 50 mM Tris-HCl buffer (pH 7.5) containing 0.15 M NaCl.…”

Section: Introductionmentioning

confidence: 99%

“…t-PA isolated from tissues [5,7] or cell culture [4] is an active enzyme that is Abbreviations: t-PA, tissue plasminogen activator; -p-NA, -p-nitro-anilide; SBTI, soybean trypsin inhibitor; LBTI, lima bean trypsin inhibitor; HMW-kininogen, high molecular mass kininogen; TBS, 50 mM Tris-HCl buffer (pH 7.5) containing 0.15 M NaCl. (Here, t-PA and vascular plasminogen activator are considered to be identical proteins.…”

Section: Introductionmentioning

confidence: 99%

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Proteolytic activation of tissue plasminogen activator by plasma and tissue enzymes

1984

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Tissue kallikrein and factor Xa were found to activate tissue plasminogen activator (t-PA) at a rate comparable with that of plasmin. During the activation reaction, the single-chain molecule was converted into a two-chain form. A slight t-PA activating activity was also found in plasma kallikrein. Other activated coagulation factors, factor XIIa, factor XIa, factor IXa, factor VIIa, thrombin and activated protein C had no effect on t-PA activation. t-PA was also activated by a tissue kallikrein-like enzyme that was isolated from the culture medium of melanoma cells. These results indicate that tissue kallikrein and factor Xa may participate in the extrinsic pathway of human fibrinolysis. Fibrinolysis t-PA Tissue kallikrein Coagulation factor

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“…The t-PA preparations isolated from uterus [5], heart [7] and melanoma cells [4] in the absence of aprotinin are principally in the two-chain form.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proteolytic activation of tissue plasminogen activator by plasma and tissue enzymes

1984

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“…Under physiological conditions, coagulation and fibrinolysis are precisely regulated and molecular links between these systems permit timely removal of ongoing or acutely induced fibrin deposits [3,4]. The major fibrinolytic protease -plasmin, is generated by activation of plasminogen (PLG) by both tissue type PLG activator (tPA) as well as by urokinase (uPA) [5,6,7]. Plasmin cleaves both tPA and uPA, transforming them from single chain forms to more Please address all correspondence to: Alexei Iakhiaev Ph.D., Assistant Professor of Biochemistry, The University of Texas Health Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, Telephone: (903) FAX: (903) 877-5627, Email: alexei.iakhiaev@uthct.edu.…”

Section: Discussionmentioning

confidence: 99%

Thrombin–thrombomodulin inhibits prourokinase-mediated pleural mesothelial cell-dependent fibrinolysis

Iakhiaev

Nalian

Koenig

et al. 2007

Thrombosis Research

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SummaryFibrin deposition is a hallmark of pleural inflammation and loculation but understanding of mechanisms by which mesothelial cells regulate intrapleural fibrinolysins remains incomplete. We speculated that pleural mesothelial cells regulate local fibrinolytic capacity via processing of single chain urokinase type plasminogen activator (scuPA). Pretreatment of human pleural mesothelial (MeT-5A) cells with TGF-β or thrombin, either alone or in combination, inhibited urokinase (uPA)-mediated fibrinolysis by MeT-5A. Thrombin, unlike TGF-β, inhibited fibrinolysis without induction of PAI-1, suggesting that thrombin-mediated cleavage of scuPA inhibits the fibrinolytic capacity of MeT-5A cells. Thrombin cleaves both purified scuPA as well as that secreted by MeT-5A cells and cell surface thrombomodulin accelerates thrombin-mediated cleavage of scuPA to inhibit cellular fibrinolytic activity. Molecular dynamics analyses demonstrated that thrombin-cleaved scuPA (uPAt) do not acquire a catalytically active conformation and that secondary plasminogen binding sites of uPA implicated in plasminogen activation are distorted in uPAt, explaining, at least in part, why uPAt is a poor enzyme. uPAt was detectable in transudative and exudative pleural effusions from patients. Intrapleural administration of scuPA generated increased levels of uPAt in PF of rabbits with pleural injury and loculation induced by tetracycline in vivo. This pathway is operative in diverse forms of pleural injury, restricts the urokinase-dependent fibrinolytic capacity of pleural mesothelial cells and contributes to local control of fibrinolytic activity via processing of endogenous or exogenous scuPA within the pleural compartment. Keywords fibrinolysis; single chain urokinase type plasminogen activator (scuPA); thrombin; thrombomodulin Fibrin deposition in the pleural space is a hallmark of inflammatory pleural disease [1,2]. Fibrin is deposited as a result of excessive activation of coagulation and insufficient fibrinolysis. Under physiological conditions, coagulation and fibrinolysis are precisely regulated and molecular links between these systems permit timely removal of ongoing or acutely induced fibrin deposits [3,4]. The major fibrinolytic protease -plasmin, is generated by activation of plasminogen (PLG) by both tissue type PLG activator (tPA) as well as by urokinase (uPA) [5,6,7]. Plasmin cleaves both tPA and uPA, transforming them from single chain forms to more Please address all correspondence to: Alexei Iakhiaev Ph.D., Assistant Professor of Biochemistry, The University of Texas Health Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, Telephone: (903) FAX: (903) 877-5627, Email: alexei.iakhiaev@uthct.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable for...

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“…64 In 1979, Rijken and coworkers isolated the first highly purified form of t-PA (1 mg) from human uterine tissue. 65 The same group further established the fact that t-PA was synthesized by the vascular endothelial cells and is secreted into the blood stream. 64 The release is of both types, i.e., constitutive and receptor-mediated occurring in response to factors of the coagulation cascade like factor Xa and thrombin.…”

Section: Second Generation Plasminogen Activatorsmentioning

confidence: 97%

The evolution of recombinant thrombolytics: Current status and future directions

Adivitiya

Khasa

2016

Bioengineered

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Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

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Purification and partial characterization of plasminogen activator from human uterine tissue

Cited by 317 publications

References 23 publications

Proteolytic activation of tissue plasminogen activator by plasma and tissue enzymes

Proteolytic activation of tissue plasminogen activator by plasma and tissue enzymes

Thrombin–thrombomodulin inhibits prourokinase-mediated pleural mesothelial cell-dependent fibrinolysis

The evolution of recombinant thrombolytics: Current status and future directions

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