Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins wit h potential antioxidant activity. Despite evidence that they are upregulate d in pulmonary tissue after oxidative stress, little is known regarding the ir influence on trace metal homeostasis. In this study, we have used copper - and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpre ssing and gene knockout mice and hyperoxia to investigate the effects of ch ronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and met allothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copp er and iron as well as circulating copper homeostasis. These results sugges t that ceruloplasmin and metallothionein may function as antioxidants indep endent of their role in trace metal homeostasis and that Cu/Zn SOD function s in copper homeostasis via mechanisms distinct from its superoxide scaveng ing properties.