Identification of dietary copper- and iron-regulated genes in rat intestine

Copper and iron act at different levels on gene expression. Due to their chemical reactivity, both metals could play a role in the regulation of the protein machinery involved in their metabolism, and/or of the metabolic function they are involved in. Experimental and clinical evidences raise also the hypothesis of the existence of genes commonly regulated by both metals. Purpose of this work was to find genes modulated by copper and iron in the rat intestine. A panel of 24 animals was randomly divided into three nutritional treatments including a control, a copper-deficient and an iron-deficient diet. The positive regulation of iron responsive element (IRE)-DMT1 gene was found, with different extent, in both experimental groups. A differential display reverse transcription (DDRT)-polymerase chain reaction (PCR) analysis carried out on the rat intestinal mRNAs demonstrated the differential expression of five cDNA fragments. Among these, the Cytochrome c oxidase (COX) subunit II mitochondrial gene resulted to be regulated by both metals, the Serum and Glucocorticoids-regulated Kinase (SGK) gene mainly by iron, and an Ebnerin-like 2 kb mRNA dramatically down-regulated by copper. Two residual clones showed low identity scores with sequences present in data bank. Finally, we observed that both iron and copper are able to modulate the expression of the three characterized genes in some tissues, other than intestine.