The loss of HIF1 α leads to increased susceptibility to cadmium-chloride-induced toxicity in mouse embryonic fibroblasts

Wild-type and hif1 α-/- mef cells were used to determine the role of hif1 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 hif1 α-/- cells. cadmium-induced cell death,however,was significantly higher in hif1 α-/- cells as compared to their wild-type counterparts. increased cell death in the hif1 α-/- 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 hif1 play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels. copyright © 2011 ajith vengellur et al.