PDF(Sci-hub)
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.
摘要：
镉（Cd2）被认为是人类致癌物，因为它会引起氧化应激并改变DNA修复反应。然而,Cd2+如何被细胞吸收尚不清楚。我们假设Cd2+可以通过膜铜（Cu）转运蛋白转运到细胞中，CTR1。CTR1表达在mRNA或蛋白质水平上不受Cd2+暴露的影响。过表达hCTR1的稳定细胞系，在人肝细胞系HepG2中，或zCTR1，在斑马鱼肝细胞系ZFL中，被创建来研究他们对Cd2+侮辱的反应。发现过表达CTR1的HepG2和ZFL细胞均具有较高的Cd2摄取，因此对Cd2敏感。相比之下,HepG2细胞中hCTR1敲低导致Cd2+的摄取减少，使细胞相对抵抗Cd2+。定位研究表明，hCTR1在Cd2+暴露后具有聚集模式，可能是为了降低Cd2+吸收和Cd2+诱导的毒性。这些体外结果表明，CTR1可以将Cd2+转运到细胞中，导致Cd2+毒性。
