Thrombolytic properties of an inactive proenzyme form of human urokinase secreted from human kidney cells.

Kasai, S; Arimura, Hirofumi; Nishida, Masayuki; Suyama, Takehiro

doi:10.1247/csf.10.151

Cited by 23 publications

(8 citation statements)

References 26 publications

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“…Fibrin-rich thrombi were prepared in plastic tubes by mixing 3 ml of the 3.8% sodium citrated plasma with 0.7 ml of 0.25 mol/L CaCl2. 18, 19 The thrombi were cut into pieces and weighed by microelectron-balancer (Sartorus GMBH, Gottingen, Germany). Other pieces were fixed by 4% formaldehyde and subjected to histopathological assessment.…”

Section: Preparation Of Thrombusmentioning

confidence: 99%

Histological Observations and the Process of Ultrasound Contrast Agent Enhancement of Tissue Plasminogen Activator Thrombolysis With Ultrasound Exposure

et al. 1999

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Section: Preparation Of Thrombusmentioning

confidence: 99%

Histological Observations and the Process of Ultrasound Contrast Agent Enhancement of Tissue Plasminogen Activator Thrombolysis With Ultrasound Exposure

et al. 1999

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“…Urokinase facilitates this process by mediating the conversion of the abundant zymogen, plasminogen, into the widely acting serine protease plasmin, the latter which degrades several extracellular matrix components including laminin, fibronectin, and possibly type IV collagen (4,5). Transcription of the urokinase gene gives rise to a 2.5-kilobase mRNA (6), which is subsequently translated into a single chain Ӎ 50-kDa proenzyme (7,8) and secreted into the extracellular space. The steady state level of urokinase mRNA is determined at two levels.…”

mentioning

confidence: 99%

Involvement of a Mitogen-activated Protein Kinase Signaling Pathway in the Regulation of Urokinase Promoter Activity by c-Ha-ras

Lengyel

Stepp

Gum

et al. 1995

Journal of Biological Chemistry

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The expression of the urokinase-type plasminogen activator, which plays a crucial role in tissue remodeling by controlling the synthesis of the broadly acting plasmin serine protease, is regulated by several tyrosine kinases. Since the actions of these tyrosine kinases is dependent on the activation of ras proteins, we undertook a study to identify signaling events downstream of ras responsible for the stimulation of urokinase promoter activity. Transient expression of an activated cHa-ras in OVCAR-3 cells, which do not harbor the mutated oncogene, led to a dose-dependent transactivation of the urokinase promoter. A sequence residing between ؊2109 and ؊1964 was critical for the stimulation of the urokinase promoter by c-Ha-ras. Mutation of an AP-1 and a PEA3 site at ؊1967 and ؊1973, respectively, or the co-expression of a transactivation domain-lacking c-jun substantially impaired the ability of c-Ha-ras to stimulate urokinase promoter activity. The induction of the urokinase promoter by ras was completely blocked by expression of a dominant negative c-raf expression vector and substantially reduced in cells made to co-express a catalytically inactive mitogen-activated protein kinase kinase. Further, the expression of an ERK1/ERK2-inactivating phosphatase (CL100) abrogated the stimulation of the urokinase promoter by c-Ha-ras. These data argue for a role of a mitogen-activated protein kinase-dependent signaling pathway in the regulation of urokinase promoter activity by ras.

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“…For example, plasmin converts Glu-plasminogen into Lys-plasminogen, which is a preferable substrate for plasminogen acti'vators that transform plasminogen to plasmin [3][4][5]. Plasmin activates pro-urokinase to active urokinase [6][7][8] and converts high-molecular-mass urokinase into low-molecular-mass urokinase [5,9]. It also re-activates complexes of plasminogen activators formed with their specific inhibitors, such as plasminogen-activator inhibitor type-l [10].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of plasmin by fibrinogen

Higazi¹,

Mayer

1990

Biochemical Journal

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The kinetics of inhibition of the amidolytic activity of plasmin on D-Val-L-Leu-L-Lys p-nitroanilide hydrochloride (S-2251) by fibrinogen and fibrin were determined. Reciprocal (1/v versus 1/[S]) plots of plasmin inhibition by 0.50 StMfibrinogen showed a non-linear downward curve. The Hill coefficient (h) was 0.68, suggesting negative co-operativity.By contrast, fibrin produced a simple competitive inhibition of plasmin (K, = 12,ug/ml). Addition of 0.1 mM-6-aminohexanoic acid shifted the non-linear curve obtained in the presence of fibrinogen to a straight line as for controls, indicating that 6-aminohexanoic acid abolishes the fibrinogen-induced inhibition. Transient exposure of the enzyme to pH 1.0 abrogates the ability of fibrinogen to inhibit plasmin activity. Acidification had no effect on the Vm.ax but increased the Km of plasmin. The present evidence for modulation of plasmin reveals a novel mechanism for control of fibrinolysis by fibrinogen, a component of the coagulation system and the precursor of the physiological substrate of plasmin. INTRODUCTIONThe fibrinolytic process, mediated through the plasminogen activation cascade, is under stringent metabolic control. Accordingly, extracellular plasminogen-activator activity is regulated at various stages, including the level of biosynthesis, secretion from producer cells, activation of inactive proenzyme forms, and interaction of different enzyme forms with activators and inhibitors [1]. The plasminogen activation cascade culminates in formation of plasmin. The non-specific and extremely potent serine protease plasmin (EC 3.4.21.7) fulfils pivotal functions in

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Thrombolytic properties of an inactive proenzyme form of human urokinase secreted from human kidney cells.

Cited by 23 publications

References 26 publications

Histological Observations and the Process of Ultrasound Contrast Agent Enhancement of Tissue Plasminogen Activator Thrombolysis With Ultrasound Exposure

Histological Observations and the Process of Ultrasound Contrast Agent Enhancement of Tissue Plasminogen Activator Thrombolysis With Ultrasound Exposure

Involvement of a Mitogen-activated Protein Kinase Signaling Pathway in the Regulation of Urokinase Promoter Activity by c-Ha-ras

Inhibition of plasmin by fibrinogen

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