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stimulation is restricted to system y+
1 Dipartimento di Medicina Sperimentale, Sezione di Patologia Generale e Clinica, Università degli Studi di Parma, 43100 Parma; and 2 Cattedra di Cardiochirurgia, Centro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico, Università degli Studi di Milano, 20122 Milan, Italy
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-
(TNF-) 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-, 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- or
lipopolysaccharide occurs exclusively through changes in CAT2B and CAT1
expression and is dissociated from stimulation of nitric oxide production.
system y+L; cationic amino acid transporters; SLC7A genes; lipopolysaccharide; nitric oxide
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