Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells.

Coleman, Patrick L.; Patel, Paresh D.; Cwikel, Bernard J.; Rafferty, U M; Sznycer-Laszuk, R; Gelehrter, Thomas D.

doi:10.1016/s0021-9258(17)35668-5

Cited by 64 publications

(6 citation statements)

References 42 publications

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“…This inhibition was observed to be second order with rate constants calculated to be 7.0 X 106 and 6.6 X 105 M"1 s'1 for trypsin and plasmin, respectively (Table I). These rate constants are between 20 and 200 times lower than those observed for either the UK/PAI-1 (Table II) or the tPA/PAI-1 interaction (Chmielewska et al, 1983;Kruifhof et al, 1986;Colucci et al, 1986;Coleman et al, 1986). In fact, the second-order rate constant calculated for the UK/PAI-1 interaction is approximately 4 times greater than that either determined by us for the single-chain tPA/PAI-1 interaction (4 X 107 M'1 s'1, data not shown) or reported by others (Coleman et al, 1986;Chmielewska et al, 1983;Kruithof et al, 1986;Colucci et al, 1986).…”

Section: Discussionmentioning

confidence: 71%

“…These rate constants are between 20 and 200 times lower than those observed for either the UK/PAI-1 (Table II) or the tPA/PAI-1 interaction (Chmielewska et al, 1983;Kruifhof et al, 1986;Colucci et al, 1986;Coleman et al, 1986). In fact, the second-order rate constant calculated for the UK/PAI-1 interaction is approximately 4 times greater than that either determined by us for the single-chain tPA/PAI-1 interaction (4 X 107 M'1 s'1, data not shown) or reported by others (Coleman et al, 1986;Chmielewska et al, 1983;Kruithof et al, 1986;Colucci et al, 1986). The UK/PAI-1 rate constant is one of the highest reported for protease-protease inhibitor interactions (Travis & Salvesen, 1983) and approaches the diffusioncontrolled limit (Fersht, 1985).…”

Section: Discussionmentioning

confidence: 71%

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Bovine plasminogen activator inhibitor 1: Specificity determinations and comparison of the active, latent, and guanidine-activated forms

Hekman¹,

Loskutoff²

1988

Biochemistry

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The plasminogen activator inhibitor 1 (PAI-1) synthesized and released by cultured bovine aortic endothelial cells is present in conditioned medium in a latent form that can be activated by guanidine hydrochloride [Hekman, C. M., & Loskutoff, D. J. (1985) J. Biol. Chem. 260, 11581-11587]. The purified, guanidine-activated PAI-1 was shown to inhibit both plasmin and trypsin in a dose- and time-dependent manner. Second-order rate constants for these interactions were calculated to be 6.6 X 10(5) and 7.0 X 10(6) M-1 s-1 for plasmin and trypsin, respectively. Experiments were conducted to compare the inherently active and the guanidine-activated forms of PAI-1. The two active forms had similar kinetic parameters for interaction with urokinase (Kd, 0.3 pM; kassoc, 1.5 X 10(8) M-1 s-1) and were both inactivated upon treatment with acid or base and by incubation at 37 degrees C. The latent form was relatively stable when incubated under similar conditions. The decrease in PAI-1 activity upon incubation at 37 degrees C was partially restored by a second treatment with guanidine hydrochloride. However, the degree of recovery decreased as a function of incubation time at 37 degrees C. These data suggest that active and guanidine-activated PAI-1 represent a single form of PAI-1. Incubation of this form at 37 degrees C yields two distinct populations of inactive PAI-1, one capable of reactivation and another that appears to be irreversibly inactivated.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 71%

Bovine plasminogen activator inhibitor 1: Specificity determinations and comparison of the active, latent, and guanidine-activated forms

Hekman¹,

Loskutoff²

1988

Biochemistry

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“…The quantities k 1 (T), k 2 (T), k 3 (T) and k 4 (T) are the rate constants governing these reactions, and contain the explicit temperature dependence of these processes. Values for k 1 (T), k 2 (T), k 3 (T) and k 4 (T) have been determined by others at T = 37 • C (Schneider and Nesheim 2004, Coleman et al 1986, Wiman and Collen 1978, Tiefenbrunn et al 1986, Wu and Diamond 1995, and are 0.011, 29, 10 and 0.77 (µM −1 s −1 ) respectively. At fixed r and T, such that r is within the region of clot lysis (figure 1), we can write the following expression from (5d) using standard chemistry nomenclature:…”

Section: Chemical Considerationsmentioning

confidence: 90%

Arrhenius temperature dependence ofin vitrotissue plasminogen activator thrombolysis

et al. 2007

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Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T ≤ 35 °C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Δm(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E eff of 42.0 ± 0.9 kJ mole −1 . E eff approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole −1 . A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.

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“…The endothelial cell inhibitor is proteolytically converted to an inactive form by u-PA (38) and it may be speculated that, apart from inhibiting PA, this inhibitor, its conversion product, or a putative released peptide may have other functions. Another exciting subject for further study is the regulation of inhibitor production; hormones and growth factors have been found to affect inhibitor levels in different cell types (1,14,15,17,19,36,40).…”

Section: Pa Inhibitors (Pal)mentioning

confidence: 99%

Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors

Blasi¹,

Vassalli²,

Danø³

1987

The Journal of Cell Biology

585

283

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Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells.

Cited by 64 publications

References 42 publications

Bovine plasminogen activator inhibitor 1: Specificity determinations and comparison of the active, latent, and guanidine-activated forms

Bovine plasminogen activator inhibitor 1: Specificity determinations and comparison of the active, latent, and guanidine-activated forms

Arrhenius temperature dependence ofin vitrotissue plasminogen activator thrombolysis

Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors

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