Abstract
Human umbilical vein endothelial cells transport arginine through two Na(+)-independent systems. System y(+)L is insensitive to N-ethylmaleimide (NEM), inhibited by L-leucine in the presence of Na(+), and referable to the expression of SLC7A6/y(+)LAT2, SLC7A7/y(+)LAT1, and SLC3A2/4F2hc. System y(+) is referable to the expression of SLC7A1/CAT1 and SLC7A2/CAT2B. Tumor necrosis factor-alpha (TNF-alpha) and bacterial lipopolysaccharide induce a transient stimulation of arginine influx and efflux through system y(+). Increased expression of SLC7A2/CAT2B is detectable from 3 h of treatment, while SLC7A1 expression is inhibited at later times of incubation. System y(+)L activity and expression remain unaltered. Nitric oxide synthase type 2 mRNA is not detected in the absence or presence of TNF-alpha, while the latter condition lowers nitric oxide synthase type 3 expression at the mRNA and the protein level. Nitrite accumulation is comparable in cytokine-treated and control cells up to 48 h of treatment. It is concluded that modulation of endothelial arginine transport by TNF-alpha or lipopolysaccharide occurs exclusively through changes in CAT2B and CAT1 expression and is dissociated from stimulation of nitric oxide production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Transport System y+ / physiology*
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Amino Acid Transport System y+L
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Amino Acid Transport Systems, Basic*
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Antineoplastic Agents / pharmacology*
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Arginine / metabolism*
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Biological Transport / drug effects
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Biological Transport / physiology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cationic Amino Acid Transporter 1 / genetics
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Cationic Amino Acid Transporter 1 / metabolism
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Cationic Amino Acid Transporter 2 / genetics
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Cationic Amino Acid Transporter 2 / metabolism
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Cells, Cultured
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DNA Primers
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism*
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Enzyme Inhibitors / pharmacology
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Ethylmaleimide / pharmacology
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Fusion Regulatory Protein 1, Light Chains / genetics
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Fusion Regulatory Protein 1, Light Chains / metabolism
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Gene Expression / drug effects
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Gene Expression / physiology
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Humans
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Lipopolysaccharides / pharmacology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Nitrites / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
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Umbilical Veins / cytology
Substances
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Amino Acid Transport System y+
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Amino Acid Transport System y+L
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Amino Acid Transport Systems, Basic
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Antineoplastic Agents
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Carrier Proteins
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Cationic Amino Acid Transporter 1
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Cationic Amino Acid Transporter 2
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DNA Primers
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Enzyme Inhibitors
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Fusion Regulatory Protein 1, Light Chains
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Lipopolysaccharides
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Membrane Proteins
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Nitrites
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SLC7A7 protein, human
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Tumor Necrosis Factor-alpha
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Slc7a2 protein, mouse
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Nitric Oxide
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Arginine
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Ethylmaleimide