Accumulation of transferrin in Caco-2 cells: A possible mechanism of intestinal transferrin absorption

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• 作者：Ching-Jou Lim ; Fariba Norouziyan ; Wei-Chiang Shen
• 关键词：Transferrin ; Transferrin receptor ; Caco-2 cells ; Accumulation ; Oral absorption
• 刊名：Journal of Controlled Release
• 出版年：2007
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：8 October 2007
• 卷：122
• 期：3
• 页码：393-398
• 文件大小：451 K

摘要

Transferrin receptor (TfR)-mediated endocytosis and transcytosis in enterocyte-like Caco-2 cells was investigated in order to elucidate the transport mechanism of orally administered Tf-fusion proteins. Cellular uptake and pulse chase studies were performed in Caco-2, MCF-7 and bladder carcinoma (5637) cells using ¹²⁵I-labeled Tf (¹²⁵I-Tf). Co-localization studies of Rab 11 and FITC–Tf endocytosed at either the apical or basolateral membrane were performed in polarized Caco-2 cells grown on Transwells, using confocal laser scanning microscopy (LSM510, Zeiss). Unlike in MCF-7 or 5637 cells, where rapid recycling of Tf was observed, a significant amount of endocytosed ¹²⁵I-Tf accumulated in Caco-2 cells. This accumulation was especially noticeable with the internalization of ¹²⁵I-Tf from the apical membrane of polarized Caco-2 cells. Confocal microscopy studies showed that apically, but not basolaterally, endocytosed FITC–Tf was delivered to a Rab11-positive compartment. Our results suggest that a significant amount of apically endocytosed Tf in intestinal epithelial cells is transported to a Rab11-positive compartment, possibly a late endosomal and slow recycling compartment. The Rab11-positive compartment may control the release of apically internalized Tf for either slow recycling to apical membrane or processing to transcytotic compartments.