Iron deficiency alters H- and L-ferritin expression in rat brain

Ferritin (Ft) H and L subunits are independently regulated proteins with both transcriptional and translational regulation in response to cellular iron levels. While the heterogeneous distribution of ferritin and iron in the brain is now well established, the relative response of each subunit to iron deficiency and iron supplementation, is not well defined. Weanling male Sprague-Dawley rats (n=12 per group) were randomly assigned to an iron deficient (3.5 mg Fe/kg diet), control (35 mg Fe/kg diet) or supplemented (350 mg Fe/kg diet) diet for six weeks. The H-/L-ferritin subunit ratio and mRNA levels were determined. Overall, the protein ratio in control rats of H to L was approximately 45:1 compared to a ratio >60:1 in iron deficiency but the absolute amounts of each subunit varied greatly from one brain region to another. The ratio of H-:L-ferritin mRNA was 6:1 and was not affected by dietary iron deficiency in contrast to a potent effect on mRNA levels in liver. Severe iron deficiency reduced brain ferritin H protein levels significantly in all regions, whereas only ferritin L levels in striatum, substantia nigra and pons were affected by iron deficiency. Supplemental dietary iron increased both ferritin subunits, with the largest increase (50%) in the hippocampus. These data indicate that ferritin H and L subunits within the brain respond differently to iron status and suggest post transcription regulation as a key event.