Heme and non-heme iron transporters in non-polarized and polarized cells.
Heme and non-heme iron transporters in non-polarized and polarized cells.
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DOI：
10.1186/1471-2121-11-39
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发表时间：
2010-06-04
期刊：
影响因子：
--
通讯作者：
Kishi F
中科院分区：
文献类型：
--
作者：
Yanatori I;Tabuchi M;Kawai Y;Yasui Y;Akagi R;Kishi F
膳食中的血红素铁和非血红素铁以及血红蛋白中的循环铁是含铁分子合成的重要产物。过量时，铁是潜在有毒的，因为它可以通过芬顿反应产生活性氧物质。人类可以吸收、运输、储存和回收铁，而不需要排泄系统来去除多余的铁。迄今为止，已经报道了两个候选血红素转运蛋白和两个铁转运蛋白。血红素加氧酶（HO）降解细胞中的血红素，铁产物被身体再利用。为了详细说明血红素的吸收和降解过程，以及铁的再利用，我们确定了这些转运蛋白和血红素氧合酶的亚细胞定位。在这项研究中，我们分析了亚细胞定位的2种同工酶的HO，4种异构体的二价金属转运蛋白1（DMT 1），和2个候选血红素转运蛋白-血红素载体蛋白1（HCP 1）和血红素反应基因-1（HRG-1）-在非极化和极化细胞。在非极化细胞中，HCP 1、HRG-1和DMT1A-I位于质膜上。在极化细胞中，它们显示出不同的定位：HCP 1和DMT1A-I位于顶膜，而HRG-1位于基底侧膜和溶酶体。发现DMT1A-I N-末端胞质结构域的16 Leu对质膜定位至关重要。HO位于滑面内质网中并与NADPH-细胞色素P450还原酶共定位。HCP 1和DMT1A-I定位于顶膜，HRG-1定位于基底外侧膜和溶酶体。这些结果表明，HCP 1和DMT1A-I具有摄取膳食血红素和非血红素铁的功能。HRG-1可以将内吞的血红素从溶酶体转运到胞质溶胶中。这些定位研究支持一种模型，其中胞质血红素可以被HO降解，并且所产生的铁通过铁转运蛋白ferroportin 1输出到组织液中，所述铁转运蛋白ferroportin 1在肠细胞的基底外侧膜中或在巨噬细胞的质膜中表达。释放的铁通过转铁蛋白转运并重新用于红系系统中的血红蛋白合成。
Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs), and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs. In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1), and 2 candidate heme transporters--heme carrier protein 1 (HCP1) and heme responsive gene-1 (HRG-1)--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase. HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is expressed in the basolateral membrane in enterocytes or in the plasma membrane in macrophages. The liberated iron is transported by transferrin and reutilized for hemoglobin synthesis in the erythroid system.
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