1. Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+).
- Author
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Sala R, Rotoli BM, Colla E, Visigalli R, Parolari A, Bussolati O, Gazzola GC, and Dall'Asta V
- Subjects
- Amino Acid Transport System y+L, Biological Transport drug effects, Biological Transport physiology, Carrier Proteins genetics, Carrier Proteins metabolism, Cationic Amino Acid Transporter 1 genetics, Cationic Amino Acid Transporter 1 metabolism, Cationic Amino Acid Transporter 2 genetics, Cationic Amino Acid Transporter 2 metabolism, Cells, Cultured, DNA Primers, Endothelium, Vascular cytology, Enzyme Inhibitors pharmacology, Ethylmaleimide pharmacology, Fusion Regulatory Protein 1, Light Chains genetics, Fusion Regulatory Protein 1, Light Chains metabolism, Gene Expression drug effects, Gene Expression physiology, Humans, Lipopolysaccharides pharmacology, Membrane Proteins genetics, Membrane Proteins metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase genetics, Nitric Oxide Synthase Type II, Nitrites metabolism, Umbilical Veins cytology, Amino Acid Transport System y+ physiology, Amino Acid Transport Systems, Basic, Antineoplastic Agents pharmacology, Arginine metabolism, Endothelium, Vascular metabolism, Tumor Necrosis Factor-alpha pharmacology
- 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.
- Published
- 2002
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