Copper deficiency increases ferroportin expression in rats

Abstract

Ferroportin is a transmembrane iron‐export protein that plays an important role in dietary iron absorption and iron recycling from senescent red blood cells. Ferroportin expression increases with tissue iron loading but decreases in response to hepcidin, the circulating iron‐regulatory hormone that binds to ferroportin, causing its internalization and degradation. Hepcidin expression increases with iron loading but decreases during anemia. We examined ferroportin and hepcidin expression in copper‐deficient (CuD) rats, which have elevated liver iron levels but are anemic. We compared CuD and copper‐adequate (CuA) animals (n=4/group) after one month of treatment postweaning. Hemoglobin levels were lower in CuD than in CuA rats (101 vs. 159 g/L). Western blot analysis revealed that ferroportin levels increased in CuD rats relative to CuA rats by 4‐ and 1.6‐fold in liver and spleen, respectively (P<0.02). Increased ferroportin expression in CuD rat tissues was associated with increased ferroportin transcript abundance, as measured by qRT‐PCR. Copy number of hepatic hepcidin mRNA was more than 50‐fold lower in CuD than CuA rats despite a doubling of liver iron. We conclude that tissue ferroportin levels increase in CuD rats because of diminished hepcidin levels and increased ferroportin mRNA abundance.