Duodenal Reductase Activity and Spleen Iron Stores Are Reduced and Erythropoiesis Is Abnormal in Dcytb Knockout Mice Exposed to Hypoxic Conditions
Duodenal Reductase Activity and Spleen Iron Stores Are Reduced and Erythropoiesis Is Abnormal in Dcytb Knockout Mice Exposed to Hypoxic Conditions
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DOI：
10.3945/jn.112.160358
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发表时间：
2012-11-01
影响因子：
4.2
通讯作者：
McKie, Andrew T.
中科院分区：
文献类型：
--
作者：
Choi, Jeehyea;Masaratana, Patarabutr;McKie, Andrew T.
十二指肠细胞色素b （Dcytb, Cybrd1）是一种定位于十二指肠的铁还原酶，在铁吸收增加的情况下高度上调。为了研究Dcytb对十二指肠总铁还原酶活性的贡献及其在铁代谢中的广泛作用，我们首先测量了野生型（WT）和Dcytb敲除（Dcytb(-/-)）小鼠在三种已知诱导肠道铁还原酶的条件下的十二指肠铁还原酶活性：饮食铁缺乏、缺氧和怀孕。将Dcytb（-/-）和WT小鼠随机分为对照组（缺铁组，饲粮铁48 mg/kg；缺氧组，常压；妊娠组，未妊娠动物）和治疗组（缺铁组，饲粮铁2-3 mg/kg；缺氧组，53.3 kPa压力；妊娠组，妊娠第20 d），测定十二指肠还原酶活性。在这些条件下，我们没有发现Dcyt（-/-）小鼠的铁还原酶活性的诱导，这表明在十二指肠中没有其他可诱导的铁还原酶存在。为了测试在红细胞生成需求增加的情况下是否需要Dcytb来吸收铁，我们还测量了缺氧条件下WT和Dcytb（-/-）小鼠的组织非血红素铁水平和血液学指标。与WT小鼠相比，暴露于缺氧的Dcytb（-/-）小鼠的铁吸收、血红蛋白或肝脏总非血红素铁没有明显改变的证据。然而，脾脏非血红素铁显著减少（6.7 +/- 1.0 vs. 12.7 +/- 0.9 nmol）。毫克组织(1);P < 0.01, n = 7-8)，低氧Dcytb（-/-）小鼠与低氧WT小鼠相比，网状红细胞血红蛋白受损，网状红细胞平均红细胞血红蛋白较低（276 +/-比283 +/- 2 g）。l - 1;P < 0.05, n = 7-8)，正常环境下Dcytb（-/-）与正常环境下WT小鼠比较。因此，我们得出结论，DCYTB是肠道中主要的铁调节十二指肠铁还原酶，并且DCYTB是最佳铁代谢所必需的。[j] .中华医学杂志。42(2):299 - 294,2012。
Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the duodenum that is highly upregulated in circumstances of increased iron absorption. To address the contribution of Dcytb to total duodenal ferric reductase activity as well as its wider role in iron metabolism, we first measured duodenal ferric reductase activity in wild-type (WT) and Dcytb knockout (Dcytb(-/-)) mice under 3 conditions known to induce gut ferric reductase: dietary iron deficiency, hypoxia, and pregnancy. Dcytb(-/-) and WT mice were randomly assigned to control (iron deficiency experiment, 48 mg/kg dietary iron; hypoxia experiment, normal atmospheric pressure; pregnancy experiment, nonpregnant animals) or treatment (iron deficiency experiment, 2-3 mg/kg dietary iron; hypoxia experiment, 53.3 kPa pressure; pregnancy experiment, d 20 of pregnancy) groups and duodenal reductase activity measured. We found no induction of ferric reductase activity in Dcyt(-/-) mice under any of these conditions, indicating there are no other inducible ferric reductases present in the duodenum. To test whether Dcytb was required for iron absorption in conditions with increased erythropoietic demand, we also measured tissue nonheme iron levels and hematological indices in WT and Dcytb(-/-) mice exposed to hypoxia. There was no evidence of gross alterations in iron absorption, hemoglobin, or total liver nonheme iron in Dcytb(-/-) mice exposed to hypoxia compared with WT mice. However, spleen nonheme iron was significantly less (6.7 +/- 1.0 vs. 12.7 +/- 0.9 nmol . mg tissue(-1); P < 0.01, n = 7-8) in hypoxic Dcytb(-/-) compared with hypoxic WT mice and there was evidence of impaired reticulocyte hemoglobinization with a lower reticulocyte mean corpuscular hemoglobin (276 +/- vs. 283 +/- 2 g . L-1; P < 0.05, n = 7-8) in normoxic Dcytb(-/-) compared with normoxic WT mice. We therefore conclude that DCYTB is the primary iron-regulated duodenal ferric reductase in the gut and that Dcytb is necessary for optimal iron metabolism. J. Nutr. 142: 1929-1934, 2012.