Cadmium induces oxidative stress and apoptosis in lung epithelial cells

Abstract

Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC₅₀ of 45 μM concentration. Cd significantly induces the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with the leakage of lactate dehydrogenase (LDH). Cells with continuous exposure of Cd deplete the antioxidant super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of the expression of genes involved in apoptosis show that both the extrinsic and intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis factor-α (TNF-α), executor caspase-8 and pro-apoptotic gene (Bax) were induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells. Fluorescence-activated cell sorting (FACS) analysis further confirms the induction of apoptosis in Cd-treated A549 cells.

Keywords:

• Cadmium
• ROS
• SOD
• Apoptosis
• FACS
• RT-PCR

Acknowledgements

Authors wish to express their gratitude to the Department of Microbiology and Biotechnology, Bangalore University, Bengaluru, for providing the DST-FIST, UGC-SAP and department facility.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

The authors wish to express their gratitude to the Department of Science and Technology-Promotion of University Research and Scientific Excellence (DST-PURSE) [SR/59/Z-23/2010/38(c)] and University Grant Commission-Center with Potential for Excellence in Particular Area (UGC-CPEPA) [8-2/2008(NS/PE)], New Delhi, for providing financial support. K. M. Kiran Kumar and M. Naveen Kumar are grateful to DST-PURSE for providing fellowships.