Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells.

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.

SUBMITTER: Kwok ML 

PROVIDER: S-EPMC7695923 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature