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The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1.

ABSTRACT: 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-1? (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-1?, 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.

SUBMITTER: Chen SY

PROVIDER: S-EPMC6834119 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1.

Chen Ssu-Yu SY Liu Shu-Ting ST Lin Wun-Rong WR Lin Chi-Kang CK Huang Shih-Ming SM

International journal of molecular sciences 20191022 20

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 ...[more]

PMID: 31652494

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The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1.

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The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1.

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