Augmentation of streptokinase activator activity by fibrinogen or fibrin

Camiolo, Sarah M.; Markus, Gabor; Evers, John L.; Hobika, G. H.

doi:10.1016/0049-3848(80)90372-2

Cited by 26 publications

(16 citation statements)

References 14 publications

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“…Studies from several laboratories showed that fibrin, fibrinogen and fragment D en hance the activity of streptokinase [12,[28][29][30][31][32], It was claimed that fibrinogen increases only the rate of formation of an active site in the SK-plasminogen complex and does not have an effect on the activator activity of the SK-plasminogen complex [30]. However, other studies [12,31,32] found that fibrino gen also stimulates the activator activity of the complex.…”

Section: Enhancement Of Streptokinase Activitymentioning

confidence: 99%

Streptokinase - Biochemistry and Clinical Application

Reddy

1988

Enzyme

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Section: Enhancement Of Streptokinase Activitymentioning

confidence: 99%

Streptokinase - Biochemistry and Clinical Application

Reddy

1988

Enzyme

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“…There have been many reports indicating that the activation of human plasminogen by streptokinase (SK) was enhanced in the pres ence of plasma factors related to fibrinogen [1][2][3][4][5][6]. We have indicated that early degrada tion products of fibrinogen enhanced the ac tivation of plasminogen by SK in the plasma and were called 'SK potentiators' [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Kinetic Analyses of Potentiation of Plasminogen Activation by Streptokinase in the Presence of Fibrin or Its Degradation Products

Takada¹,

Takada²

1987

Pathophysiol Haemos Thromb

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When Glu-plasminogen (Glu-plg) was activated by various amounts of streptokinase (SK), K_m of the hydrolysis of S-2251 by the mixture of Glu-plg and SK did not change, but V_max increased with an increase in the amount of SK. Since low concentrations of SK-plg complex do not result in its conversion to the SK-plasmin complex by mutual activation, these results seem to suggest that the SK-plg complex may be a better activator when S-2251 is used as a substrate. When Glu-plg was activated by SK in the presence of fibrin(ogen) or its degradation products (potentiating agents), K_m did not change with an increase in the concentration of each potentiating agent, but V_max increased. The effects of potentiating agents on the k_cat values of these activators were in the order of fibrin > fibrinogen > D > E.

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“…It has been established that the SK-induced activation rate of human Glu,Pg is stimulated by fibrinogen (8)(9)(10)20) and inhibited by Cl" (14)(15)(16). We have shown that both effectors function by the respective stimulation (20) or inhibition (15) Here, SK and HPg interact to form a stoichiometric complex (SK-HPg), from which, most likely via conformational altera tions, a complex, SK-HPg*, is formed, that possesses plasminogen activator activity.…”

Section: Resultsmentioning

confidence: 99%

“…Fibrinogen, fibrin and degradation products of these proteins function as positive effec tors of plasminogen activation with tPA and SK as activators (7)(8)(9)(10). On the other hand, anions inhibit the activation of human plasminogen with all of the above activators (11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Control of Human Plasminogen Activation

Castellino¹,

Urano²,

Serrano³

et al. 1988

Pathophysiol Haemos Thromb

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The activation of GlU₁-plasminogen (Glu-Pg) by streptokinase (SK), urokinase (UK) and tissue plasminogen activator (tPA) is under rigorous control by molecules such as ε-aminocaproic acid (EACA), fibrinogen (Fg), fibrin (Fn) and, as we have recently discovered, anions. This presentation will focus on the biochemical mechanisms that are involved in these processes. In the case of activation by SK, a species of activator complex, composed of Glu-Pg and SK, can be identified that is inhibited by anions, such as C1^–, and stimulated by Fg and Fn. This species rapidly decays to another activator complex, also consisting of Glu-Pg and SK, that is much less sensitive to control by these effector molecules. The most stable activator complex, containing equimolar SK and plasmin, is not affected to a great extent by anions, Fg or Fn. In the overall activation of Glu-Pg by SK, C1^– behaves as a mixed inhibitor, with a Ki of 6.4–9.2 mM, and Fg functions as a mixed activator, displaying a Ka of 110–240 nM. These results show that activation of Glu-Pg by SK in physiological samples would be considerably inhibited by C1^– in the absence of Fg. The activation of Glu-Pg by both high- and low-molecular weight UK is also inhibited by C1^–, but is stimulated by EACA. The inhibition by C1^– does not occur in the presence of concentrations of EACA that saturate its weak binding sites on Glu-Pg, and the stimulation by EACA is maximally exhibited in the presence of C1^–. The anion inhibitory effect follows a Hofmeister series, as does the binding (stimulatory) constant of EACA to Glu-Pg. Based upon structural studies of Glu-Pg in the presence of a variety of anions, we find that Glu-Pg can adopt a conformation that is optimal to activation and one that is not. The former occurs in the presence of weakly bound anions, or in the presence of any salt, plus saturating levels of EACA. The latter conformation is adopted in the presence of tightly bound anions. Anions also influence the rate of Glu-Pg activation by tPA, and the stimulation of this process by Fg and Fn. The mechanism of this effect is currently under investigation.

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Augmentation of streptokinase activator activity by fibrinogen or fibrin

Cited by 26 publications

References 14 publications

Streptokinase - Biochemistry and Clinical Application

Streptokinase - Biochemistry and Clinical Application

Kinetic Analyses of Potentiation of Plasminogen Activation by Streptokinase in the Presence of Fibrin or Its Degradation Products

Control of Human Plasminogen Activation

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