| Protease nexin-1 inhibits plasminogen activation-induced apoptosis of adherent cells. | |
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MedLine Citation:
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PMID: 14699093 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Degradation of adhesive glycoproteins by plasmin is implicated in cell migration. In this study, we further explored the role of plasminogen activation in cell adhesion and survival and show that uncontrolled plasminogen activation at the cell surface may induce cell detachment and apoptosis. We hypothesized that this process could be prevented in adherent cells by expression of protease nexin-1, a potent serpin able to inhibit thrombin, plasmin, and plasminogen activators. Using two- and three-dimensional culture systems, we demonstrate that Chinese hamster ovary fibroblasts constitutively express tissue-type plasminogen activator and efficiently activate exogenously added plasminogen in a specific and saturable manner (K(m) = 46 nm). The formation of plasmin results in proteolysis of fibronectin and laminin, which is followed by cell detachment and apoptosis. Protease nexin-1 expressed by transfected cells significantly inhibited the activity of plasmin and tissue-type plasminogen activator via the formation of inhibitory complexes and prevented cell detachment and apoptosis. In conclusion, protease nexin-1 may be an important anti-apoptotic factor for adherent cells. This cell model could be a useful tool to evaluate therapeutic agents such as serpins in vascular pathologies involving pericellular protease-protease inhibitor imbalance. |
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Authors:
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Patrick Rossignol; Benoît Ho-Tin-Noé; Roger Vranckx; Marie-Christine Bouton; Olivier Meilhac; H Roger Lijnen; Marie-Claude Guillin; Jean-Baptiste Michel; Eduardo Anglés-Cano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-12-29 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-03-08 Completed Date: 2004-05-19 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 10346-56 Citation Subset: IM |
Affiliation:
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INSERM U460, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris 18, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Protein Precursor Animals Anoikis* Apoptosis* CHO Cells Carrier Proteins / physiology* Caspases / metabolism Cell Adhesion Cell Culture Techniques Cell Division Cell Survival Cell-Free System Cricetinae DNA / chemistry DNA Fragmentation Dose-Response Relationship, Drug Fibronectins / chemistry Humans Immunoblotting In Situ Nick-End Labeling Kinetics Laminin / chemistry Matrix Metalloproteinase 9 / metabolism Plasminogen / chemistry, metabolism* Plasminogen Activator Inhibitor 1 / metabolism Receptors, Cell Surface Time Factors Transfection Urokinase-Type Plasminogen Activator / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein Precursor; 0/Carrier Proteins; 0/Fibronectins; 0/Laminin; 0/Plasminogen Activator Inhibitor 1; 0/Receptors, Cell Surface; 0/protease nexins; 9001-91-6/Plasminogen; 9007-49-2/DNA; EC 3.4.21.73/Urokinase-Type Plasminogen Activator; EC 3.4.22.-/Caspases; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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