Kim Heejeong, Son Hwa-Young, Bailey Sarah M, Lee Jaekwon
Redox Biology Center, Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G356-64. doi: 10.1152/ajpgi.90632.2008. Epub 2008 Dec 18.
Copper is a vital trace element required for normal growth and development of many organisms. To determine the roles for copper transporter 1 (Ctr1) in hepatic copper metabolism and the contribution of the liver to systemic copper homeostasis, we have generated and characterized mice in which Ctr1 is deleted specifically in the liver. These mice express less than 10% residual Ctr1 protein in the liver and exhibit a small but significant growth retardation, which disappears with age. Hepatic copper concentrations and the activities of copper-requiring enzymes are reduced; however, mild copper deficiency relative to Ctr1 protein deficit indicates compensatory mechanisms for copper metabolism. Copper concentrations of other organs did not alter despite the defect in hepatic copper uptake. Whereas biliary copper excretion is reduced, urinary copper concentration in these mice is higher than that of control mice. Our data indicate that Ctr1 plays a critical role in copper acquisition in the liver, and, when Ctr1 expression is compromised, compensatory mechanisms facilitate copper uptake and/or retention in the liver and excretion of copper via urine.
铜是许多生物体正常生长和发育所需的重要微量元素。为了确定铜转运蛋白1（Ctr1）在肝脏铜代谢中的作用以及肝脏对全身铜稳态的贡献，我们构建并鉴定了肝脏特异性缺失Ctr1的小鼠。这些小鼠肝脏中残余的Ctr1蛋白表达量不到10%，并表现出轻微但显著的生长迟缓，这种迟缓会随着年龄增长而消失。肝脏铜浓度和需铜酶的活性降低；然而，相对于Ctr1蛋白缺乏而言，轻度的铜缺乏表明存在铜代谢的补偿机制。尽管肝脏摄取铜存在缺陷，但其他器官的铜浓度并未改变。虽然胆汁铜排泄减少，但这些小鼠的尿铜浓度高于对照小鼠。我们的数据表明，Ctr1在肝脏获取铜的过程中起关键作用，并且当Ctr1表达受损时，补偿机制有助于肝脏摄取和/或保留铜，并通过尿液排泄铜。
