Enhancement of plasminogen activation by surfactin C: augmentation of fibrinolysis in vitro and in vivo.

Abstract

The reciprocal activation of plasminogen and prourokinase (pro-u-PA) is an important mechanism in the initiation and propagation of local fibrinolytic activity. We have found that a bacterial lipopeptide compound, surfactin C (3-20 microM), enhances the activation of pro-u-PA in the presence of plasminogen. This effect accompanied increased conversions of both pro-u-PA and plasminogen to their two-chain forms. Surfactin C also elevated the rate of plasminogen activation by two-chain urokinase (tcu-PA) while not affecting plasmin-catalyzed pro-u-PA activation and amidolytic activities of tcu-PA and plasmin. The intrinsic fluorescence of plasminogen was increased, and molecular elution time of plasminogen in size-exclusion chromatography was shortened in the presence of surfactin C. These results suggested that surfactin C induced a relaxation of plasminogen conformation, thus leading to enhancement of u-PA-catalyzed plasminogen activation, which in turn caused feedback pro-u-PA activation. Surfactin C was active in enhancing [125I]fibrin degradation both by pro-u-PA/plasminogen and tcu-PA/plasminogen systems. In a rat pulmonary embolism model, surfactin C (1 mg/kg, i.v.) elevated 125I plasma clot lysis when injected in combination with pro-u-PA. The present results provide first evidence that pharmacological relaxation of plasminogen conformation leads to enhanced fibrinolysis in vivo.

• Authors: Tadashi Kikuchi, Keiji Hasumi
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1596 Issue 2 Pg. 234-45 (Apr 29 2002) ISSN: 0006-3002 [Print] Netherlands
• PMID: 12007605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopeptides
• Lipoproteins
• Peptides, Cyclic
• Recombinant Proteins
• surfactin peptide
• Fibrin
• Plasminogen
• Urokinase-Type Plasminogen Activator
• saruplase

Topics

• Animals
• Bacillus
• Fibrin (chemistry)
• Fibrinolysis (drug effects)
• Lipopeptides
• Lipoproteins (administration & dosage, pharmacology)
• Male
• Molecular Structure
• Peptides, Cyclic (administration & dosage, chemistry, pharmacology)
• Plasminogen (chemistry)
• Protein Conformation
• Pulmonary Embolism (drug therapy)
• Rats
• Rats, Wistar
• Recombinant Proteins (administration & dosage, chemistry)
• Urokinase-Type Plasminogen Activator (administration & dosage, chemistry)