Caco-2 cell acquisition of dietary iron(III) invokes a nanoparticulate endocytic pathway.
Caco-2 cell acquisition of dietary iron(III) invokes a nanoparticulate endocytic pathway.
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DOI：
10.1371/journal.pone.0081250
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Powell JJ
中科院分区：
文献类型：
--
作者：
Pereira DI;Mergler BI;Faria N;Bruggraber SF;Aslam MF;Poots LK;Prassmayer L;Lönnerdal B;Brown AP;Powell JJ
膳食中的非血红素铁含有亚铁[Fe(II)]和铁[Fe(III)]两种铁组分，后者在从酸性胃进入酸性较弱的十二指肠时应水解，形成铁（III）氧-氢氧化物颗粒。利用模拟体内水解环境的条件，我们证实形成了纳米分散的精细水合铁样颗粒。这些合成的类似物（水动力直径~ 10 nm）很容易粘附在分化的Caco-2细胞的细胞膜上，并通过透射电镜观察到内化过程。此外，ccao -2暴露于这些纳米颗粒导致细胞形成铁蛋白（即铁利用），与可溶性铁不同，铁蛋白的形成通过抑制网格蛋白介导的内吞作用而减少（p=0.02）。模拟溶酶体消化表明，纳米颗粒在温和的酸性条件下很容易与溶酶体配体柠檬酸盐溶解。这在细胞培养中得到证实，莫能菌素以剂量依赖性的方式抑制Caco-2对铁的利用（p<0.05），而可溶性铁再次不受影响。我们的研究结果揭示了小肠上皮获取膳食铁（III）的内吞途径的可能性，这将补充已建立的可溶铁（II）的DMT-1途径。
Dietary non-heme iron contains ferrous [Fe(II)] and ferric [Fe(III)] iron fractions and the latter should hydrolyze, forming Fe(III) oxo-hydroxide particles, on passing from the acidic stomach to less acidic duodenum. Using conditions to mimic the in vivo hydrolytic environment we confirmed the formation of nanodisperse fine ferrihydrite-like particles. Synthetic analogues of these (~ 10 nm hydrodynamic diameter) were readily adherent to the cell membrane of differentiated Caco-2 cells and internalization was visualized using transmission electron microscopy. Moreover, Caco-2 exposure to these nanoparticles led to ferritin formation (i.e., iron utilization) by the cells, which, unlike for soluble forms of iron, was reduced (p=0.02) by inhibition of clathrin-mediated endocytosis. Simulated lysosomal digestion indicated that the nanoparticles are readily dissolved under mildly acidic conditions with the lysosomal ligand, citrate. This was confirmed in cell culture as monensin inhibited Caco-2 utilization of iron from this source in a dose dependent fashion (p<0.05) whilet soluble iron was again unaffected. Our findings reveal the possibility of an endocytic pathway for acquisition of dietary Fe(III) by the small intestinal epithelium, which would complement the established DMT-1 pathway for soluble Fe(II).
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DOI：
10.1152/ajprenal.00359.2005
发表时间：
2006-06-01
影响因子：
4.2
作者：
Abouhamed, M;Gburek, J;Smith, CP
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Brodin, B
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作者：
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