Down-regulation of ABCG2 and ABCB4 transporters in the placenta of rats exposed to cadmium

// Lili Liu 1, 2 , Liang Zhou 1 , Shuiwang Hu 3 , Shanyu Zhou 2 , Yingyu Deng 2 , Ming Dong 2 , Jianxun Huang 2 , Yuli Zeng 2 , Xiaoyan Chen 2 , Na Zhao 2 , Hongling Li 2 , Zhenhua Ding 1 1 Department of Radiation Medicine, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou, China 2 Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China 3 Department of Pathophysiology, Southern Medical University, Guangzhou, China Correspondence to: Zhenhua Ding, email: dingzh@fimmu.com Keywords: cadmium, proteomics, placenta, ABCG2, ABCB4 Received: March 19, 2016      Accepted: April 27, 2016      Published: May 17, 2016 ABSTRACT As a maternal and developmental toxicant, cadmium (Cd) possesses weak penetrability through the placental barrier. However, the underlying mechanism remains unclear. To gain insight into the protein molecules associated with Cd toxicity in placenta and explore their roles in Cd transportation, a reproductive animal experiment was carried out using Sprague-Dawley rats. We performed proteomic analysis of the placenta by Difference Gel Electrophoresis (DIGE) combined with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS). The DIGE assay identified 15 protein spots that were differentially expressed with a greater than 1.5-fold change in placenta of Cd-treated rats compared to the control rats. Based on the expression patterns and biological functions of the proteins, we selected the ABCG2 and ABCB4 transporter proteins for further analysis. Western blot analysis showed that Cd exposure could down-regulate the expression of ABCG2 and ABCB4 in the placenta. There was a negative dose-response relationship between Cd exposure and the expression of ABCG2 or ABCB4 protein. These results indicated that down-regulation of ABCG2 and ABCB4 transporters may regulate Cd across through placenta and thus affect the in vivo toxic effect of Cd to fetus.