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Toxicol In Vitro. 2016 Aug;34:146-152. doi: 10.1016/j.tiv.2016.04.001. Epub 2016 Apr 9.

ROS-dependent HMGA2 upregulation mediates Cd-induced proliferation in MRC-5 cells.

Author information

1
Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
2
Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China; Jilin Province Research Institute for Tuberculosis Prevention and Treatment, No. 3145. Jing yang Road, Changchun 130062, China.
3
Liaoning Anti-Degenerative Diseases Natural Products Engineering Technology Research Center, Dalian Medical University, Dalian 116044, China.
4
Dalian Municipal Center for Disease Control and Prevention, Dalian 116023, China.
5
Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China. Electronic address: caojunly@163.com.

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 (2μM) for 48h 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.

KEYWORDS:

Cadmium; Cell cycle; Cell proliferation; HMGA2; MRC-5 cells; ROS

PMID:
27071802
DOI:
10.1016/j.tiv.2016.04.001
[Indexed for MEDLINE]

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