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The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1
Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834119/ https://www.ncbi.nlm.nih.gov/pubmed/31652494 http://dx.doi.org/10.3390/ijms20205225 |
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author | Chen, Ssu-Yu Liu, Shu-Ting Lin, Wun-Rong Lin, Chi-Kang Huang, Shih-Ming |
author_facet | Chen, Ssu-Yu Liu, Shu-Ting Lin, Wun-Rong Lin, Chi-Kang Huang, Shih-Ming |
author_sort | Chen, Ssu-Yu |
collection | PubMed |
description | Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Copper sulfate also increased the levels of apoptosis, senescence, mitochondrial dysfunction, autophagy, ROS, and the expression of several stress proteins, including ATF3, c-Fos, DEC1 (differentiated embryonic chondrocyte gene 1), p21, p53, and HIF-1α (hypoxia-inducible factor 1 alpha). The suppression of copper-induced ROS generation by the ROS scavenger N-acetyl cysteine verified copper’s functional role, while the suppression of copper’s effects by the copper chelator disulfiram, confirmed its specificity. Selective induction of HIF-1α, p53, and phosphorylated ERK proteins by copper was blocked by the knockdown of the transcription factor DEC1, suggesting copper’s effects are mediated by DEC1. In addition to HeLa cells, copper also exerted cytotoxic effects in human endometrial (HEC-1-A) and lung (A549) adenocarcinoma cells, but not in normal human kidney (HEK293) or bronchial (Beas-2B) epithelial cells. These findings shed new light on the functional roles of copper within cells. |
format | Online Article Text |
id | pubmed-6834119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68341192019-11-25 The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 Chen, Ssu-Yu Liu, Shu-Ting Lin, Wun-Rong Lin, Chi-Kang Huang, Shih-Ming Int J Mol Sci Article Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Copper sulfate also increased the levels of apoptosis, senescence, mitochondrial dysfunction, autophagy, ROS, and the expression of several stress proteins, including ATF3, c-Fos, DEC1 (differentiated embryonic chondrocyte gene 1), p21, p53, and HIF-1α (hypoxia-inducible factor 1 alpha). The suppression of copper-induced ROS generation by the ROS scavenger N-acetyl cysteine verified copper’s functional role, while the suppression of copper’s effects by the copper chelator disulfiram, confirmed its specificity. Selective induction of HIF-1α, p53, and phosphorylated ERK proteins by copper was blocked by the knockdown of the transcription factor DEC1, suggesting copper’s effects are mediated by DEC1. In addition to HeLa cells, copper also exerted cytotoxic effects in human endometrial (HEC-1-A) and lung (A549) adenocarcinoma cells, but not in normal human kidney (HEK293) or bronchial (Beas-2B) epithelial cells. These findings shed new light on the functional roles of copper within cells. MDPI 2019-10-22 /pmc/articles/PMC6834119/ /pubmed/31652494 http://dx.doi.org/10.3390/ijms20205225 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Ssu-Yu Liu, Shu-Ting Lin, Wun-Rong Lin, Chi-Kang Huang, Shih-Ming The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title | The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title_full | The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title_fullStr | The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title_full_unstemmed | The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title_short | The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1 |
title_sort | mechanisms underlying the cytotoxic effects of copper via differentiated embryonic chondrocyte gene 1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834119/ https://www.ncbi.nlm.nih.gov/pubmed/31652494 http://dx.doi.org/10.3390/ijms20205225 |
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