Copper Transporter 2 Content Is Lower in Liver and Heart of Copper-Deficient Rats
Copper Transporter 2 Content Is Lower in Liver and Heart of Copper-Deficient Rats
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DOI：
10.3390/ijms11114741
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发表时间：
2010-11-01
影响因子：
5.6
通讯作者：
L'Abbe, Mary R.
中科院分区：
文献类型：
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作者：
Bertinato, Jesse;Duval, Sebastien;L'Abbe, Mary R.
铜转运蛋白2(Ctr2)是一种跨膜蛋白，可以跨细胞膜转运铜并增加胞内铜水平。使用细胞系的实验表明，Ctr2的表达受铜状态的调节。最近的研究表明，细胞中较低的Ctr2含量会增加细胞对含铂癌症药物的摄取，并增加药物的毒性，这突显了Ctr2表达变化的重要性。在这项研究中，我们研究了体内营养性铜缺乏是否改变了Ctr2的表达。测定了正常(CuN)、中度缺铜(CuM)和缺铜(CuD)饲料喂养的大鼠肝脏和心脏中Ctr2mRNA和蛋白的表达。与铜氮大鼠相比，饲喂铜缺乏饲料的大鼠肝脏Ctr2蛋白的表达呈剂量依赖性下降。Ctr2蛋白在铜-M和铜-D大鼠中分别降低42%和85%。CuD大鼠肝脏Ctr2基因表达水平降低50%，而CuM大鼠肝脏Ctr2基因表达未受影响。在心脏中，Ctr2蛋白仅在铜-D大鼠中降低(低46%)。这些数据表明，体内铜缺乏会降低Ctr2的含量。
Copper (Cu) transporter 2 (Ctr2) is a transmembrane protein that transports Cu across cell membranes and increases cytosolic Cu levels. Experiments using cell lines have suggested that Ctr2 expression is regulated by Cu status. The importance of changes in Ctr2 expression is underscored by recent studies demonstrating that lower Ctr2 content in cells increases the cellular uptake of platinum-containing cancer drugs and toxicity to the drugs. In this study, we examined whether Ctr2 expression is altered by a nutritional Cu deficiency in vivo. Ctr2 mRNA and protein in liver and heart from rats fed a normal (Cu-N), moderately deficient (Cu-M) or deficient (Cu-D) Cu diet was measured. Rats fed the Cu-deficient diets showed a dose-dependent decrease in liver Ctr2 protein compared to Cu-N rats. Ctr2 protein was 42% and 85% lower in Cu-M and Cu-D rats, respectively. Liver Ctr2 mRNA was 50% lower in Cu-D rats and unaffected in Cu-M rats. In heart, Ctr2 protein was only lower in Cu-D rats (46% lower). These data show that Cu deficiency decreases Ctr2 content in vivo.