Broderius Margaret A, Prohaska Joseph R
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School, Duluth, MN 55812, USA.
Nutr Res. 2009 Jul;29(7):494-502. doi: 10.1016/j.nutres.2009.06.006.
Sensitive blood biochemical markers of dietary copper status are not yet known. Rat models were used to investigate the response of severe copper deficiency in dams and pups by comparing abundance of several cuproproteins in erythrocytes, white blood cells, and platelets. The hypothesis tested was that copper deficiency would result in changes in abundance of cuproproteins in blood cells. Copper-deficient (CuD) Holtzman dams and pups had signs consistent with severe copper deficiency compared with copper-adequate controls including lower liver copper and hemoglobin levels and near total loss of plasma ceruloplasmin diamine oxidase activity. Copper-deficient erythrocytes had lower copper, zinc superoxide dismutase (SOD1) but higher copper metallochaperone for SOD1 (CCS) compared with copper-adequate, resulting in higher CCS/SOD1 levels. This ratio was more sensitive in CuD erythrocytes than CuD white cells and especially in CuD platelets. However, both white blood cells and platelets from CuD dams and pups had nearly nondetectable levels of cytochrome c oxidase subunit IV. Because isolation of relatively pure populations of erythrocytes and platelets is feasible, and reagents for immunoblot methods are available, determination of CCS/SOD1 and cytochrome c oxidase subunit IV protein levels may be useful to assess copper status of humans.
目前尚不清楚饮食中铜状态的敏感血液生化标志物。通过比较红细胞、白细胞和血小板中几种铜蛋白的丰度，利用大鼠模型研究母鼠和幼鼠严重铜缺乏的反应。所检验的假设是铜缺乏会导致血细胞中铜蛋白丰度的变化。与铜充足的对照组相比，铜缺乏（CuD）的霍尔兹曼母鼠和幼鼠有与严重铜缺乏一致的体征，包括肝脏铜和血红蛋白水平较低以及血浆铜蓝蛋白二胺氧化酶活性几乎完全丧失。与铜充足的红细胞相比，铜缺乏的红细胞铜、锌超氧化物歧化酶（SOD1）含量较低，但SOD1的铜金属伴侣蛋白（CCS）含量较高，导致CCS/SOD1水平较高。该比值在CuD红细胞中比在CuD白细胞中更敏感，在CuD血小板中尤其敏感。然而，来自CuD母鼠和幼鼠的白细胞和血小板中细胞色素c氧化酶亚基IV的水平几乎检测不到。由于分离相对纯净的红细胞和血小板群体是可行的，并且有免疫印迹方法所需的试剂，因此测定CCS/SOD1和细胞色素c氧化酶亚基IV的蛋白质水平可能有助于评估人类的铜状态。
