CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages
CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages
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DOI：
10.1042/0264-6021:3400549
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发表时间：
1999-06-01
影响因子：
4.1
通讯作者：
Markovich, D
中科院分区：
文献类型：
--
作者：
Kakuda, DK;Sweet, MJ;Markovich, D
激活的巨噬细胞需要摄取L精氨酸来维持NO的合成。几个运输系统可以调节这种L精氨酸的流入。通过竞争分析和基因表达研究，确定了氨基酸转运系统yt是该酶活性的主要载体。为了确定已知的四个y(+)转运系统基因中的哪一个与巨噬细胞诱导的L精氨酸摄取有关，我们使用了非洲爪哇卵母细胞的杂交耗竭研究。阳离子氨基酸转运体(CAT)2反义寡核苷酸可阻断活化巨噬细胞诱导的L精氨酸转运。结合表达研究证明，随着L精氨酸摄取的增加，CAT2的mRNA和蛋白水平升高，我们的数据表明，CAT2介导了激活的J774巨噬细胞产生升高的NO所必需的L精氨酸转运。
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 yt 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.