Food Science & Human Nutrition Department, University of Florida, Gainesville, 32611, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G877-86. doi: 10.1152/ajpgi.00261.2011. Epub 2011 Aug 18.
The Menkes copper ATPase (Atp7a) and metallothionein (Mt1a) are induced in the duodenum of iron-deficient rats, and serum and hepatic copper levels increase. Induction of a multi-copper ferroxidase (ceruloplasmin; Cp) has also been documented. These findings hint at an important role for Cu during iron deficiency. The intestinal divalent metal transporter 1 (Dmt1) is also induced during iron deficiency. The hypothesis that Dmt1 is involved in the copper-related compensatory response during iron deficiency was tested, utilizing a mutant Dmt1 rat model, namely the Belgrade (b/b) rat. Data from b/b rats were compared with phenotypically normal, heterozygous +/b rats. Intestinal Atp7a and Dmt1 expression was increased in b/b rats, whereas Mt1a expression was unchanged. Serum and liver copper levels did not increase in the Belgrades nor did Cp protein or activity. The lack of fully functional Dmt1 may thus partially blunt the compensatory response to iron deficiency by 1) decreasing copper levels in enterocytes, as exemplified by a lack of Mt1a induction and a lesser induction of Atp7a, 2) abolishing the frequently described increase in liver and serum copper, and 3) attenuating the documented increase in Cp expression and activity.
Menkes 铜 ATP 酶（Atp7a）和金属硫蛋白（Mt1a）在缺铁大鼠的十二指肠中被诱导表达，血清和肝脏铜水平升高。也有文献报道诱导产生了一种多铜氧化酶（铜蓝蛋白；Cp）。这些发现提示铜在缺铁期间可能发挥着重要作用。肠道二价金属转运蛋白 1（Dmt1）在缺铁期间也被诱导表达。本研究利用 Belgrade（b/b）突变大鼠模型（一种 Dmt1 突变大鼠模型）来检测 Dmt1 是否参与缺铁相关的代偿反应这一假说。将 b/b 大鼠的数据与表型正常的杂合子+/b 大鼠进行比较。b/b 大鼠的肠道 Atp7a 和 Dmt1 表达增加，而 Mt1a 表达不变。Belgrade 大鼠的血清和肝脏铜水平没有增加，Cp 蛋白或活性也没有增加。因此，缺乏完全功能的 Dmt1 可能会通过以下方式部分削弱对缺铁的代偿反应：1）降低肠细胞中的铜水平，例如缺乏 Mt1a 诱导和 Atp7a 诱导程度降低，2）消除经常描述的肝脏和血清铜增加，3）减弱文献报道的 Cp 表达和活性增加。
