Diabetes and Nutritional Sciences Division, School of Biomedical and Health Sciences, King’s College, London, UK.
J Nutr. 2012 Nov;142(11):1929-34. doi: 10.3945/jn.112.160358. Epub 2012 Sep 18.
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 Dcytb(-/-) 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 ± 1 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.
十二指肠细胞色素 b（Dcytb，Cybrd1）是一种定位于十二指肠的三价铁还原酶，在铁吸收增加的情况下高度上调。为了确定 Dcytb 对十二指肠总三价铁还原酶活性的贡献及其在铁代谢中的更广泛作用，我们首先在三种已知可诱导肠道三价铁还原酶的情况下测量了野生型（WT）和 Dcytb 敲除（Dcytb（-/-））小鼠的十二指肠铁还原酶活性：缺铁、缺氧和妊娠。Dcytb（-/-）和 WT 小鼠被随机分配到对照（缺铁实验，48mg/kg 饮食铁；缺氧实验，正常大气压力；妊娠实验，非妊娠动物）或治疗（缺铁实验，2-3mg/kg 饮食铁；缺氧实验，53.3kPa 压力；妊娠实验，妊娠第 20 天）组，并测量十二指肠还原酶活性。我们发现，在这些条件下，Dcytb（-/-）小鼠的铁还原酶活性没有被诱导，这表明十二指肠中没有其他可诱导的三价铁还原酶。为了测试在增加红细胞生成需求的情况下 Dcytb 是否需要铁吸收，我们还测量了暴露于缺氧的 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、血红蛋白或总肝非血红素铁没有明显变化。然而，与缺氧 WT 小鼠相比，缺氧 Dcytb（-/-）小鼠的脾脏非血红素铁明显减少（6.7±1.0 与 12.7±0.9nmol·mg 组织（-1）；P<0.01，n=7-8），并且在正常氧 Dcytb（-/-）中存在网织红细胞血红蛋白化受损的证据，其网织红细胞平均红细胞血红蛋白（276±1 与 283±2g·L（-1）；P<0.05，n=7-8）低于正常氧 WT 小鼠。因此，我们得出结论，DCYTB 是肠道中主要的铁调节十二指肠三价铁还原酶，Dcytb 是最佳铁代谢所必需的。
