Exploration of the copper-related compensatory response in the Belgrade rat model of genetic iron deficiency
Exploration of the copper-related compensatory response in the Belgrade rat model of genetic iron deficiency
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DOI：
10.1152/ajpgi.00261.2011
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Collins, James F.
中科院分区：
文献类型：
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作者：
Jiang, Lingli;Ranganathan, Perungavur;Collins, James F.
Jiang L，Ranganathan P，Lu Y，Kim C，柯林斯JF.在遗传性铁缺乏的贝尔格莱德大鼠模型中探索铜相关的代偿反应。美国生理学杂志胃肠和肝脏生理学301：G877-G886，2011年。首次发表于2011年8月18日; doi：10.1152/ajpgi.00261.2011。门克斯铜ATP酶（Atp7a）和金属硫蛋白（Mt1a）的诱导在十二指肠铁缺乏大鼠，血清和肝脏铜水平增加。还记录了多铜铁氧化酶（血浆铜蓝蛋白; Cp）的诱导。这些发现暗示了铜在缺铁过程中的重要作用。肠道二价金属转运蛋白1（Dmt1）也在缺铁期间被诱导。利用突变型Dmt 1大鼠模型，即Belgrade（B/B）大鼠，检验了Dmt 1参与铁缺乏期间铜相关代偿反应的假设。将来自B/B大鼠的数据与表型正常的杂合+/B大鼠进行比较。B/B大鼠肠Atp7 a和Dmt 1表达增加，而Mt 1 a表达不变。血清和肝脏铜水平没有增加贝尔格莱德也没有Cp蛋白或活动。因此，缺乏全功能的Dmt 1可能通过以下方式部分减弱对缺铁的代偿反应：1）降低肠上皮细胞中的铜水平，如缺乏Mt1a诱导和较少的Atp7a诱导，2）消除经常描述的肝脏和血清铜增加，3）减弱记录的Cp表达和活性增加。
Jiang L, Ranganathan P, Lu Y, Kim C, Collins JF. Exploration of the copper-related compensatory response in the Belgrade rat model of genetic iron deficiency. Am J Physiol Gastrointest Liver Physiol 301: G877-G886, 2011. First published August 18, 2011; doi:10.1152/ajpgi.00261.2011.-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.