Mild copper deficiency alters gene expression of proteins involved in iron metabolism.
Iron and copper homeostasis share common proteins and are therefore closely linked to each other. For example, copper-containing proteins like ceruloplasmin and hephaestin oxidize Fe(2+) during cellular export processes for transport in the circulation bound to transferrin. Indeed, copper deficiency provokes iron metabolism disorders leading to anemia and liver iron accumulation. The aim of the present work was to understand the cross-talk between copper status and iron metabolism. For this purpose we have established dietary copper deficiency in C57BL6 male mice during twelve weeks. Hematological parameters, copper and iron status were evaluated. cDNA microarray studies were performed to investigate gene expression profiles of proteins involved in iron metabolism in the liver, duodenum and spleen. Our results showed that copper deficiency induces microcytic and hypochromic anemia as well as liver iron overload. Gene expression profiles, however, indicate that hepatic and intestinal mRNA expression neither compensates for hepatic iron overload nor the anemia observed in this mouse model. Instead, major modifications of gene expression occurred in the spleen. We observed increased mRNA levels of the transferrin receptors 1 and 2 and of several proteins involved in the heme biosynthesis pathway (ferrochelatase, UroD, UroS,...). These results suggest that copper-deficient mice respond to the deficiency induced anemia by an adaptation leading to an increase in erythrocyte synthesis.
Auclair
Sylvain
S
Centre de Recherche en Nutrition Humaine d'Auvergne, Unité des Maladies Métaboliques et Micronutriments, INRA, Theix, 63122 St Genès Champanelle, France.
Feillet-Coudray
Christine
C
Coudray
Charles
C
Schneider
Susanne
S
Muckenthaler
Martina U
MU
Mazur
Andrzej
A
D018798:Anemia, Iron-Deficiency / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006418:Heme / Q000096:biosynthesis*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009928:Organ Specificity
D006418:Heme; D003300:Copper; D007501:Iron