Expression and regulation of endothelial nitric oxide synthase by vascular endothelial growth factor in ECV 304 cells. 2002

Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Korea. pjs@medical.yeungnam.ac.kr

Nitric oxide (NO) seems to play a pivotal role in the vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation. This study was designed to investigate the role and intracellular signal pathway of endothelial nitric oxide synthase (eNOS) activation induced by VEGF. ECV 304 cells were treated with VEGF(165) and then cell proliferation, eNOS protein and mRNA expression levels were analyzed to elucidate the functional role of eNOS in cell proliferation induced by VEGF. After exposure of cells to VEGF(165), eNOS activity and cell growth were increased by approximately two-fold in the VEGF(165) -treated cells compared to the untreated cells. In addition, VEGF stimulated eNOS expression at both the mRNA and protein levels in a dose-dependent manner. Phosphatidylinositol-3 kinase (PI-3K) inhibitors were used to assess PI-3K involvement in eNOS regulation. LY294002 was found to attenuate VEGF-stimulated eNOS expression. Wortmannin was not as effective as LY294002, but the reduction effect was detectable. Cells activated by VEGF showed increased ERK1/2 levels. Moreover, the VEGF-induced eNOS expression was reduced by the PD98059, MAPK pathway inhibitor. This suggests that eNOS expression might be regulated by PI-3K and the ERK1/2 signaling pathway. In conclusion, VEGF(165) induces ECV 304 cell proliferation via the NO produced by eNOS. In addition, eNOS may be regulated by the PI-3K or mitogen-activated protein kinase pathway.

UI MeSH Term Description Entries
D008222 Lymphokines Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. Lymphocyte Mediators,Mediators, Lymphocyte
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D016228 Endothelial Growth Factors These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences. Endothelial Cell-Derived Growth Factors,alpha-Endothelial Growth Factor,beta-Endothelial Growth Factor,ECDGF,Endo-GF,Endothelial Growth Factor,Endothelial Growth Factor Polypeptides,Endothelial Cell Derived Growth Factors,Growth Factor, Endothelial,Growth Factor, alpha-Endothelial,Growth Factor, beta-Endothelial,Growth Factors, Endothelial,alpha Endothelial Growth Factor,beta Endothelial Growth Factor
D042442 Vascular Endothelial Growth Factors A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. VEGFs
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular

Related Publications

Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
March 1999, Cardiovascular research,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
January 2010, WebmedCentral,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
January 2009, The Journal of craniofacial surgery,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
October 2001, Cornea,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
August 2001, Brain research,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
February 2001, Japanese journal of pharmacology,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
January 2016, Journal of biological regulators and homeostatic agents,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
September 2009, Hypertension (Dallas, Tex. : 1979),
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
December 2002, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons,
Jong Seon Park, and Gu Ru Hong, and Suk Whan Baek, and Dong Gu Shin, and Young Jo Kim, and Bong Sup Shim
June 2010, The Journal of biological chemistry,
Copied contents to your clipboard!