Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+).
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.
Sala
Roberto
R
Dipartimento di Medicina Sperimentale, Sezione di Patologia Generale e Clinica, Università degli Studi di Parma, 43100 Parma, Italy.
Rotoli
Bianca Maria
BM
Colla
Emanuela
E
Visigalli
Rossana
R
Parolari
Alessandro
A
Bussolati
Ovidio
O
Gazzola
Gian C
GC
Dall'Asta
Valeria
V
D027182:Amino Acid Transport System y+ / Q000502:physiology*; D027241:Amino Acid Transport System y+L; D026923:Amino Acid Transport Systems, Basic; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D026923:Amino Acid Transport Systems, Basic; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D017931:DNA Primers; D004791:Enzyme Inhibitors; D027301:Fusion Regulatory Protein 1, Light Chains; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009573:Nitrites; C421261:SLC7A7 protein, human; D014409:Tumor Necrosis Factor-alpha; C087435:Slc7a2 protein, mouse; D009569:Nitric Oxide; D001120:Arginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D005033:Ethylmaleimide