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CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages.
Kakuda DK
,
Sweet MJ
,
Mac Leod CL
,
Hume DA
,
Markovich D
.
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Activated macrophages require l-arginine uptake to sustain NO synthesis. Several transport systems could mediate this l-arginine influx. Using competition analysis and gene-expression studies, amino acid transport system y+ was identified as the major carrier responsible for this activity. To identify which of the four known y+ transport-system genes is involved in macrophage-induced l-arginine uptake, we used a hybrid-depletion study in Xenopus oocytes. Cationic amino acid transporter (CAT) 2 antisense oligodeoxyribonucleotides abolished the activated-macrophage-mRNA-induced l-arginine transport. Together with expression studies documenting that CAT2 mRNA and protein levels are elevated with increased l-arginine uptake, our data demonstrate that CAT2 mediates the l-arginine transport that is required for the raised NO production in activated J774 macrophages.
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