L-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes
L-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes
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DOI：
10.1182/blood-2005-08-3166
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Tamai, I
中科院分区：
文献类型：
--
作者：
Shima, Y;Maeda, T;Tamai, I
在本研究中，我们研究了转运L-精氨酸、L-赖氨酸、L-鸟氨酸和L-组氨酸的阳离子氨基酸转运蛋白1在造血中的作用。用逆转录聚合酶链式反应检测单个核细胞(MNC)中人CAT1(HCAT1)基因的表达水平。在血糖素A阳性的红系细胞中，CAT1的表达是未分离的单核细胞(对照)的8倍。K562细胞对L-精氨酸的摄取特征与CAT1细胞相似，表现在饱和动力学、钠非依赖性和Y(+)氨基酸转运体的特异性抑制剂N-乙基马来酰亚胺对L-精氨酸摄取的抑制作用。去除培养液中的L-精氨酸抑制K562细胞的增殖和分化，而去除L-赖氨酸或L-组氨酸对K562细胞的分化几乎没有影响，但抑制了细胞的增殖。人脐血造血祖细胞在不含L精氨酸的条件下不能发育为红系细胞。这些发现表明hCAT1通过其输入L-精氨酸的作用参与了红系造血，而精氨酸似乎是红细胞分化所必需的。
In the present study, we examined the role in hematopoiesis of cationic amino acid transporter 1 (CAT1), which transports L-arginine, L-Iysine, L-ornithine, and L-histidine. The expression level of human CAT1 (hCAT1) mRNA in mononuclear cells (MNCs) fractionated according to lineage-selective markers was examined by reverse transcriptase-polymerase chain reaction. The expression of CAT1 in glycophorin A-positive erythroid cells was 8 times higher than in nonfractionated MNC (control) cells. Characteristics of L-arginine uptake by K562 cells, an established leukemic cell line used as an erythrold model, were similar to those of CAT1 in regards to saturation kinetics, sodium independence, and substantial inhibition of L-arginine uptake by N-ethylmaleimide, which is a specific inhibitor of system y(+) amino acid transporter. Removal of L-arginine from the culture medium prevented both proliferation and differentiation of K562 cells, while removal of L-lysine or L-histidine had little effect on differentiation, though proliferation was blocked. Hematopoletic stem cells obtained from human cord blood failed to develop into erythrold cells in the absence of L-arginine in the culture medium. These findings indicate that hCAT1 is involved in erythroid hematopotesis through its role in importing L-arginine, which appears to be essential for the differentiation of red blood cells.