Evidence for a Role of p38 Kinase in Hypoxia-inducible Factor 1-independent Induction of Vascular Endothelial Growth Factor Expression by Sodium Arsenite
| Autor: | Monique C.A. Duyndam, Elsken van der Wall, Saskia Hulscher, Epie Boven, Herbert M. Pinedo |
|---|---|
| Přispěvatelé: | VU University medical center |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Vascular Endothelial Growth Factor A
MAPK/ERK pathway Time Factors Sodium arsenite Endothelial Growth Factors p38 Mitogen-Activated Protein Kinases Biochemistry Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Tumor Cells Cultured Enzyme Inhibitors Phosphorylation Arsenic trioxide Luciferases Mitogen-Activated Protein Kinase 1 Lymphokines Mitogen-Activated Protein Kinase 3 Vascular Endothelial Growth Factors Kinase Nuclear Proteins Sodium Compounds Up-Regulation Cell biology DNA-Binding Proteins Vascular endothelial growth factor Vascular endothelial growth factor A Intercellular Signaling Peptides and Proteins Hypoxia-Inducible Factor 1 Mitogen-Activated Protein Kinases Subcellular Fractions Arsenites p38 mitogen-activated protein kinases Blotting Western Enzyme-Linked Immunosorbent Assay Biology Transfection Geneeskunde Ribonucleases Animals Humans Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinase 8 RNA Messenger Protein kinase A Molecular Biology JNK Mitogen-Activated Protein Kinases Cell Biology Fibroblasts Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Kinetics chemistry Transcription Factors |
| Zdroj: | The journal of biological chemistry, 278(9), 6885. The American Society for Biochemistry and Molecular Biology Duyndam, M C A, Hulscher, ST, van der Wall, E, Pinedo, H M & Boven, E 2003, ' Evidence for a role of p38 kinase in hypoxia-inducible factor 1-independent induction of vascular endothelial growth factor expression by sodium arsenite. ', Journal of Biological Chemistry, vol. 278, no. 9, pp. 6885-95 . https://doi.org/10.1074/jbc.M206320200 Journal of Biological Chemistry, 278(9), 6885-95. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0021-9258 |
| Popis: | Recently we have demonstrated that sodium arsenite induces the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and vascular endothelial growth factor (VEGF) in OVCAR-3 human ovarian cancer cells. We now show that arsenic trioxide, an experimental anticancer drug, exerts the same effects. The involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK) pathways in the effects of sodium arsenite was investigated. By using kinase inhibitors in OVCAR-3 cells, both effects of sodium arsenite were found to be independent of phosphatidylinositol 3-kinase and p44/p42 MAPKS but were attenuated by inhibition of p38 MAPK. A role for p38 in the regulation of HIF-1alpha and VEGF expression was supported further by analysis of activation kinetics. Experiments in mouse fibroblast cell lines, lacking expression of c-Jun N-terminal kinases 1 and 2, suggested that these kinases are not required for induction of HIF-1alpha protein and VEGF mRNA. Unexpectedly, sodium arsenite did not activate a HIF-1-dependent reporter gene in OVCAR-3 cells, indicating that functional HIF-1 was not induced. In agreement with this hypothesis, up-regulation of VEGF mRNA was not reduced in HIF-1alpha(-/-) mouse fibroblast cell lines. Altogether, these data suggest that not HIF-1, but rather p38, mediates induction of VEGF mRNA expression by sodium arsenite. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|