Kakuda D K, Sweet M J, Mac Leod C L, Hume D A, Markovich D
Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, Australia.
Biochem J. 1999 Jun 1;340 ( Pt 2)(Pt 2):549-53.
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.
活化的巨噬细胞需要摄取L-精氨酸来维持一氧化氮(NO)的合成。几种转运系统可能介导这种L-精氨酸的流入。通过竞争分析和基因表达研究,氨基酸转运系统y+被确定为负责此活性的主要载体。为了确定四个已知的y+转运系统基因中的哪一个参与巨噬细胞诱导的L-精氨酸摄取,我们在非洲爪蟾卵母细胞中进行了杂交缺失研究。阳离子氨基酸转运体(CAT)2反义寡脱氧核糖核苷酸消除了活化巨噬细胞mRNA诱导的L-精氨酸转运。结合记录表明随着L-精氨酸摄取增加CAT2 mRNA和蛋白质水平升高的表达研究,我们的数据表明CAT2介导了活化的J774巨噬细胞中升高的NO产生所需的L-精氨酸转运。