A fragment of human TrpRS as a potent antagonist of ocular angiogenesis
| Autor: | David A. Cheresh, Michael I. Dorrell, Karla L. Ewalt, Karen Kinder, Atsushi Otani, John Hood, Bonnie M. Slike, Paul Schimmel, Martin Friedlander |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis Angiogenesis Inhibitors Tryptophan-tRNA Ligase Endothelial Growth Factors Plasma protein binding Biology law.invention Neovascularization Mice law medicine Animals Humans Lymphokines Mice Inbred BALB C Binding Sites Microscopy Confocal Multidisciplinary Dose-Response Relationship Drug Neovascularization Pathologic Vascular Endothelial Growth Factors Alternative splicing Antagonist Retinal Vessels Biological Sciences Molecular biology Recombinant Proteins Protein Structure Tertiary Cell biology Alternative Splicing Drug Combinations Vascular endothelial growth factor A Recombinant DNA Proteoglycans Collagen Laminin medicine.symptom Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:178-183 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Pathological angiogenesis contributes directly to profound loss of vision associated with many diseases of the eye. Recent work suggests that human tyrosyl- and tryptophanyl-tRNA synthetases (TrpRS) link protein synthesis to signal transduction pathways including angiogenesis. In this study, we show that a recombinant form of a COOH-terminal fragment of TrpRS is a potent antagonist of vascular endothelial growth factor-induced angiogenesis in a mouse model and of naturally occurring retinal angiogenesis in the neonatal mouse. The angiostatic activity is dose-dependent in both systems. The recombinant fragment is similar in size to one generated naturally by alternative splicing and can be produced by proteolysis of the full-length protein. In contrast, the full-length protein is inactive as an antagonist of angiogenesis. These results suggest that fragments of TrpRS, as naturally occurring and potentially nonimmunogenic anti-angiogenics, can be used for the treatment of neovascular eye diseases. |
| Databáze: | OpenAIRE |
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