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Journal of Toxicology
Volume 2011, Article ID 391074, 14 pages
Research Article

The Loss of HIF1 Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts

1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA
2Center for Mitochondrial Sciences and Medicine, Michigan State University, East Lansing, MI, USA
3Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA

Received 5 January 2011; Revised 13 April 2011; Accepted 5 May 2011

Academic Editor: Jack Ng

Copyright © 2011 Ajith Vengellur et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Wild-type and HIF1α −/− MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α −/− cells. Cadmium-induced cell death, however, was significantly higher in HIF1α −/− cells as compared to their wild-type counterparts. Increased cell death in the HIF1α −/− cells was correlated with lower metallothionein protein, elevated levels of reactive oxygen species, and decreased superoxide dismutase enzyme activity. The total and oxidized glutathione levels, and, correspondingly, lipid peroxidation levels were elevated in the null cells compared to wild-type cells, indicating increased antioxidant demand and greater oxidative stress. Overall, the results suggest that basal levels of HIF1α play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels.