Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells
| Autor: | Zhen Ping Li, King Ming Chan, Man Long Kwok, Tin Yu Samuel Law |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
CTR1
High-affinity Cu-uptake protein 1 Health Toxicology and Mutagenesis Cell Cadmium toxicity ybx1 Y box-binding protein 1 gene 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences 03 medical and health sciences min minutes 0302 clinical medicine Cu Copper lcsh:RA1190-1270 hCtr1 Human CTR1 gene LC50 Median lethal concentration medicine Carcinogen zCtr1 Zebrafish CTR1 gene 0105 earth and related environmental sciences lcsh:Toxicology. Poisons ComputingMethodologies_COMPUTERGRAPHICS Gene knockdown Chemistry Liver cell fungi Regular Article hCTR1 Human CTR1 protein zCTR1 Zebrafish CTR1 protein qPCR Quantitative real-time PCR Cadmium uptake PBS Phosphate-buffered saline In vitro Cell biology medicine.anatomical_structure Cell culture Toxicity Copper transporter Cd Cadmium h hours 030217 neurology & neurosurgery Oxidative stress Stable cell line |
| Zdroj: | Toxicology Reports Toxicology Reports, Vol 7, Iss, Pp 1564-1570 (2020) |
| ISSN: | 2214-7500 |
| Popis: | Graphical abstract Highlights • CTR1-overexpressing HepG2 and ZFL cell lines were created. • CTR1 overexpression in both HepG2 and ZFL cells increased Cd2+ uptake and toxicity. • CTR1 knockdown in HepG2 cells decreased Cd2+ uptake and toxicity. • CTR1 plays a significant role in Cd2+ uptake and toxicity. Cadmium (Cd2+) is considered a human carcinogen as it causes oxidative stress and alters DNA repair responses. However, how Cd2+ is taken up by cells remains unclear. We hypothesized that Cd2+ could be transported into cells via a membrane copper (Cu) transporter, CTR1. CTR1 expression was not affected by Cd2+ exposure at the mRNA or protein level. Stable cell lines overexpressing either hCTR1, in the human liver cell line HepG2, or zCTR1, in the zebrafish liver cell line ZFL, were created to study their responses to Cd2+ insult. It was found that both HepG2 and ZFL cells overexpressing CTR1 had higher Cd2+ uptake and thus became sensitive to Cd2+. In contrast, hCTR1 knockdown in HepG2 cells led to a reduced uptake of Cd2+, making the cells relatively resistant to Cd2+. Localization studies revealed that hCTR1 had a clustered pattern after Cd2+ exposure, possibly in an attempt to reduce both Cd2+ uptake and Cd2+-induced toxicity. These in vitro results indicate that CTR1 can transport Cd2+ into the cell, resulting in Cd2+ toxicity. |
| Databáze: | OpenAIRE |
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