Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells.
Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells.
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DOI：
10.1016/j.bbrc.2012.04.008
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发表时间：
2012-05-11
影响因子：
3.1
通讯作者：
Vulpe CD
中科院分区：
文献类型：
--
作者：
Lee SM;Attieh ZK;Son HS;Chen H;Bacouri-Haidar M;Vulpe CD
虽然脊椎动物的肠细胞铁进入采用多种途径，包括血红素和非血红素途径，但铁从这些细胞的排出仅通过唯一已知的转运蛋白ferroportin。性连锁贫血小鼠肠道铁输出减少暗示铁氧化酶hephaestin参与了这一过程。极化细胞暴露于两种不同的环境。肠细胞通过细胞的顶面接触肠腔，并通过基底外侧表面接触身体。以往的研究表明，局部和全身控制铁的吸收。我们假设，在顶端和/或基底侧表面的铁的可用性的差异可能会通过细胞定位的hephaestin调节铁的摄取。因此，我们的特点是本地化的hephaestin在两个模型的极化上皮细胞系，MDCK和Caco 2，不同的铁的可用性在顶端和基底侧表面。我们的研究结果表明，无论细胞的铁状态如何，在非极化细胞和缺铁和极化细胞中，hephaestin都表达在核上区室中。在极化细胞中，我们发现顶端铁（如FeSO 4）和基底侧铁（如脱辅基转铁蛋白与全转铁蛋白的比率）都会影响核上区室中肝啡肽的动员。我们发现，顶端铁的存在是必不可少的hephaestin的重新定位到一个细胞隔室中的密切接近，但不重叠的基底外侧表面。表面生物素化研究表明，在基底外侧位置的hephaestin是可访问的细胞外环境。这些结果支持了这一假设，即肝啡肽参与铁动员铁从肠循环。
While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO4) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a cellular compartment in close proximity but not overlapping with the basolateral surface. Surface biotinylation studies indicate that hephaestin in the peribasolateral location is accessible to the extra-cellular environment. These results support the hypothesis that hephaestin is involved in iron mobilization of iron from the intestine to circulation.
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影响因子：
29.4
作者：
Yeh, Kwo-Yih;Yeh, Mary;Glass, Jonathan
通讯作者：
Glass, Jonathan
影响因子：
20.3
作者：
Chen, HJ;Su, T;Vulpe, CD
通讯作者：
Vulpe, CD
影响因子：
4.2
作者：
Chen, HJ;Huang, G;Vulpe, CD
通讯作者：
Vulpe, CD
DOI：
10.1016/s0300-9629(96)00403-3
发表时间：
1997-09-01
影响因子：
2.3
作者：
Kakuta, K;Orino, K;Watanabe, K
通讯作者：
Watanabe, K
影响因子：
4
作者：
Han, Okhee;Kim, Eun-Young
通讯作者：
Kim, Eun-Young