IGF-I-induced VEGF expression in HUVEC involves phosphorylation and inhibition of poly(ADP-ribose)polymerase
| Autor: | Stefan Beckert, Stephan Coerper, Heinz Scheuenstuhl, Alfred Königsrainer, M. Zamirul Hussain, Rummana Aslam, Farshid Farrahi, Q. Perveen Ghani, Thomas K. Hunt |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
Umbilical Veins Angiogenesis Poly ADP ribose polymerase Biophysics Poly(ADP-ribose) Polymerase Inhibitors Biochemistry chemistry.chemical_compound Humans Protein phosphorylation Insulin-Like Growth Factor I Phosphorylation Molecular Biology Protein kinase C Cells Cultured Dose-Response Relationship Drug Chemistry Endothelial Cells Cell Biology Molecular biology Vascular endothelial growth factor Enzyme Activation Vascular endothelial growth factor A Gene Expression Regulation Signal transduction Poly(ADP-ribose) Polymerases |
| Zdroj: | Biochemical and biophysical research communications. 341(1) |
| ISSN: | 0006-291X |
| Popis: | Insulin-like growth factor-I (IGF-I) has been shown to promote angiogenesis by enhancing vascular endothelial growth factor (VEGF) expression. However, how IGF-I-induces VEGF expression is not yet fully understood. With this investigation, we propose a new possible mechanism involving downregulation of poly(ADP-ribosyl)ation (pADPR). We first demonstrated that IGF-I increased VEGF protein expression in endothelial cells. Inhibitors of mitogen activated kinase (PD 98059), phosphatidyl-3-inositol-kinase (LY 294002), and protein kinase C (staurosporine) diminished the IGF-I effect suggesting the involvement of signal transduction. Since there is an established link between pADPR and transcriptional activity, we focused on a possible role of poly(ADP-ribose)polymerase (PARP). The inhibition of PARP by 3-aminobenzamide or nicotinamide enhanced VEGF expression. Additionally, IGF-I markedly decreased PARP activity. Furthermore, the IGF-I-mediated inhibition of PARP could be demonstrated as a result of protein phosphorylation since phosphorylation of PARP decreased its activity in vitro and IGF-I treatment of endothelial cells induced PARP phosphorylation. The IGF-I-mediated phosphorylation and inhibition of PARP represent a novel mechanism of VEGF protein expression. |
| Databáze: | OpenAIRE |
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