Antioxidant enzyme gene transcription in copper-deficient rat liver

Antioxidant enzymes, Cu/Zn- and Mn-superoxide dismutase, catalase, and glutathione peroxidase, constitute an important defense mechanism against cytotoxicity of reactive oxygen species. Copper is essential for the activity of Cu/Zn-superoxide dismutase. Oxidative stress, therefore, is expected in organs of rats fed copper-deficient diet due to reduced Cu/Zn-superoxide dismutase activity. Our previous studies have shown that the expression of antioxidant enzymes was altered in copper-deficient rat liver. The present report was undertaken to study further the transcription of these enzymes in liver nuclei of rats made copper-deficient for 4 weeks. While copper deficiency decreased the copper in liver by about 80%, it did not alter the copper content in liver nuclei. In spite of a 100% elevation in nuclear iron concentration, liver nuclei from copper-deficient rats showed normal appearance. The transcriptional rates for Cu/Zn-superoxide dismutase, glutathione peroxidase, and glyceraldehyde-3-phosphate dehydrogenase were not altered by dietary copper deprivation. In contrast, transcriptional rates for Mn-superoxide dismutase and β-actin were increased but that for catalase was reduced in the nuclei isolated from the copperdeficient rat liver. These results suggest that oxidative stress, resulting from copper deficiency, differentially modulates the gene transcription for the antioxidant enzymes in rat liver.