PUBLICATION
Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells
- Authors
- Kwok, M.L., Li, Z.P., Law, T.Y.S., Chan, K.M.
- ID
- ZDB-PUB-201210-4
- Date
- 2020
- Source
- Toxicology reports 7: 1564-1570 (Journal)
- Registered Authors
- Chan, King-Ming
- Keywords
- CTR1, High-affinity Cu-uptake protein 1, Cadmium toxicity, Cadmium uptake, Cd, Cadmium, Copper transporter, Cu, Copper, LC50, Median lethal concentration, PBS, Phosphate-buffered saline, Stable cell line, h, hours, hCTR1, Human CTR1 protein, hCtr1, Human CTR1 gene, min, minutes, qPCR, Quantitative real-time PCR, ybx1, Y box-binding protein 1 gene, zCTR1, Zebrafish CTR1 protein, zCtr1, Zebrafish CTR1 gene
- MeSH Terms
- none
- PubMed
- 33294387 Full text @ Toxicol Rep
Citation
Kwok, M.L., Li, Z.P., Law, T.Y.S., Chan, K.M. (2020) Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells. Toxicology reports. 7:1564-1570.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping