ROS-dependent HMGA2 upregulation mediates Cd-induced proliferation in MRC-5 cells. (August 2016)

• Record Type: Journal Article
• Authors: Xie, Huaying; Wang, Jiayue; Jiang, Liping; Geng, Chengyan; Li, Qiujuan; Mei, Dan; Zhao, Lian; Cao, Jun
• Is Part Of: Toxicology in vitro. Volume 34(2016)
• Page Start: 146
• Page End: 152
• Publication Date: 2016-08
• Subjects: Cadmium -- MRC-5 cells -- HMGA2 -- ROS -- Cell proliferation -- Cell cycle; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.04.001
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Cadmium (Cd) is a heavy metal widely found in a number of environmental matrices, and the exposure to Cd is increasing nowadays. In this study, the role of high mobility group A2 (HMGA2) in Cd-induced proliferation was investigated in MRC-5 cells. Exposure to Cd (2 μM) for 48 h significantly enhanced the growth of MRC-5 cells, increased reactive oxygen species (ROS) production, and induced both mRNA and protein expression of HMGA2. Evidence for Cd-induced reduction of the number of G0/G1 phase cells and an increase in the number of cells in S phase and G2/M phase was sought by flow cytometric analysis. Western blot analysis showed that cyclin D1, cyclin B1, and cyclin E were upregulated in Cd-treated cells. Further study revealed that N -acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of MRC-5 cells, ROS generation, and the increasing protein level of HMGA2. Silencing of HMGA2 gene by siRNA blocked Cd-induced cyclin D1, cyclin B1, and cyclin E expression and reduction of the number of G0/G1 phase cells. Combining, our data showed that Cd-induced ROS formation provoked HMGA2 upregulation, caused cell cycle changes, and led to cell proliferation. This suggests that HMGA2 might be an important biomarker in Cd-induced cell proliferation. Graphical abstract: Highlights: HMGA2 plays an important role in Cd-induced cell cycle disorder and proliferation in MRC-5 cells. ROS formation might be a prerequisite for Cd-induced HMGA2 upregulation. HMGA2 might be an important biomarker in Cd-induced cell proliferation and other toxicities