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Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype

Smith, CL; Birdsey, GM; Anthony, S; Arrigoni, FI; Leiper, JM; Vallance, P; (2003) Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype. Biochemical and Biophysical Research Communications , 308 (4) 984 - 989.

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Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor, S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation

Type:Article
Title:Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype
Additional information:DA - 20030820 IS - 0006-291X LA - eng PT - Journal Article RN - 0 (Drug Combinations) RN - 0 (Endothelial Growth Factors) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Laminin) RN - 0 (Lymphokines) RN - 0 (Plasmids) RN - 0 (Proteoglycans) RN - 0 (RNA, Messenger) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - 119978-18-6 (matrigel) RN - 30315-93-6 (N,N-dimethylarginine) RN - 74-79-3 (Arginine) RN - 9007-34-5 (Collagen) RN - EC 3.5. (Amidohydrolases) RN - EC 3.5.3.18 (dimethylargininase) SB - IM SB - S
Keywords:ACID, activity, Amidohydrolases, analogs & derivatives, Arginine, biosynthesis, Blotting, Northern, cardiovascular, cell, CELLS, Cells, Cultured, Cellular, chemistry, Collagen, COMBINATION, cytology, DRUG, Drug Combinations, effects, endogenous, Endothelial, endothelial cell, endothelial cells, Endothelial Growth Factors, ENDOTHELIAL-CELLS, Endothelium, Vascular, enhanced, expression, factors, formation, growth, GROWTH FACTOR, growth factors, GROWTH-FACTOR, GROWTH-FACTORS, IM, Immunoblotting, in vitro, In-vitro, INCREASE, INCREASES, INHIBITOR, Intercellular Signaling Peptides and Proteins, LA, LAMININ, LESS, LEVEL, Lymphokines, metabolism, model, mRNA, murine, nitric oxide, nitric oxide synthase, NITRIC-OXIDE, OXIDE, pathology, peptide, Peptides, pharmacology, Phenotype, phenotypes, plasmid, Plasmids, PROTEIN, Proteins, PROTEOGLYCAN, Proteoglycans, Rna, RNA, Messenger, S, Support, Non-U.S.Gov't, SYNTHASE, Time Factors, Transfection, TUBE, Umbilical Veins, vascular, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, VEGF, vein, VITRO
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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