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Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells

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Abstract

High cellular zinc concentrations lead to impairments in ATP synthesis and cell cycle control particularly in neurons and epithelial cells. The molecular basis for these dysfunctions is still not fully elucidated. Here we analyzed the effects of a high zinc exposure (10 ppm) on gene and protein expression in the human epithelial cell line HT-29. Of the 1176 genes analyzed with cDNA arrays, nine differentially expressed genes were identified. Proteome analysis based on 1310 detected proteins identified 11 molecular targets. Most of the identified genes/proteins have not been linked to cellular zinc status before (e.g. PEC-60, R-ras3). More than half of the targets participate in ATP production or stress response. Therefore, it appears that higher zinc concentrations mediate their effects mainly via impairments in cellular energy metabolism and stress response.

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Abbreviations

CDF:

cation diffusion facilitator

cDNA:

complementary DNA

2D-PAGE:

two-dimensional polyacrylamide gel electrophoresis

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

MALDI-TOF-MS:

matrix assisted laser desorption ionization-time of flight-mass spectrometry

MT:

metallothionein

NADH:

nicotinamide adenine dinucleotide

ROS:

reactive oxygen species

ZIP:

Zrt-, Irt-like protein

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Correspondence to Hannelore Daniel.

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This work was in part supported by the Degussa Bio Actives GmbH, Freising-Weihenstephan, Germany.

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Kindermann, B., Döring, F., Fuchs, D. et al. Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells. Biometals 18, 243–253 (2005). https://doi.org/10.1007/s10534-005-1247-y

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