Differentiation- and polarization-dependent zinc tolerance in Caco-2 cells

Purpose Enterocytes are feasibly confronted with enormous zinc concentrations especially as a result of oral zinc supplementation. In the present study, we investigated the mechanisms underlying the exceptional ability to withstand this usually toxic load using the enterocytic cell line Caco-2. Meth...

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Bibliographic Details
Published in:European journal of nutrition 2011-08, Vol.50 (5), p.379-386
Main Authors: Zemann, Nina, Zemann, Adolf, Klein, Petra, Elmadfa, Ibrahim, Huettinger, Manfred
Format: Article
Language:English
Subjects:
Biological and medical sciences
Caco-2 Cells
Carrier Proteins - metabolism
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Cell Differentiation
Chemistry
Chemistry and Materials Science
Down-Regulation
Enterocytes - cytology
Enterocytes - drug effects
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Humans
Intestines - metabolism
Metallothionein - genetics
Metallothionein - metabolism
Nutrition
Original Contribution
RNA, Messenger - genetics
RNA, Messenger - metabolism
Up-Regulation
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Zinc - analysis
Zinc - metabolism
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Summary:Purpose Enterocytes are feasibly confronted with enormous zinc concentrations especially as a result of oral zinc supplementation. In the present study, we investigated the mechanisms underlying the exceptional ability to withstand this usually toxic load using the enterocytic cell line Caco-2. Methods By MTT test analysis, we compared zinc tolerance in undifferentiated Caco-2 cells (udCaco-2) and differentiated Caco-2 cells (dCaco-2). By RT-PCR, we compared the respective baseline expression levels of certain zinc transporters and metallothioneins (MTs) as well as the regulation of these components in response to high zinc concentrations. Moreover, using dCaco-2 cells cultured on porous membranes, we explored zinc tolerance in dependence of the side of zinc administration: apical versus basolateral. Results dCaco-2 cells tolerate significantly higher levels of zinc compared to udCaco-2 cells. This adaptation was accompanied by upregulated ZnT-1 and downregulated ZIP1 levels. The expression of metallothioneins MT1A and MT1X was also significantly downregulated during differentiation. Moreover, apparent from profound differences in zinc tolerance between apical and basolateral zinc application, polarization was concluded to have substantial impact on cellular zinc tolerance. Conclusions The profound increase in zinc tolerance we found in differentiated enterocyte-type Caco-2 cells and in particular, the impact of polarization are likely to reflect the physiologically indispensable capability of enterocytes to cope with remarkable concentrations of intestinal zinc.
ISSN:1436-6207
1436-6215
DOI:10.1007/s00394-010-0146-3