A novel ferritin heavy chain messenger ribonucleic acid in the human brain

Abstract

In the aging human brain, the concentrations of iron and its major storage protein, ferritin, rise but the distribution of metal and protein remains non-uniform. More ferritin could be isolated from the brains of humans who died of Alzheimer's disease (AD) than from age-and sex-matched controls. Also, brain ferritin of rats chronically exposed to aluminum chloride in their drinking water contained more aluminum and iron. Based on these earlier observations, a more detailed study of human brain ferritin was initiated. The results showed that ferritin is a component of neuritic (senile) plaques in AD. Ferritin obtained from normal or AD brains is composed of 24 subunits (70% heavy (H) chain; 30% light (L) chain). With high performance liquid chromatography, the subunits resolved into a cluster of four H-chain peaks and one major L-chain peak. Western blot analysis confirmed the identity of H- and L-fractions. The techniques of molecular biology revealed the presence of an additional ferritin messenger ribonucleic acid (mRNA) species for the H subunit which was more abundant in the brain than in other human tissues. It contained the entire sequence of 919 nucleotides of H chain mRNA from liver but also an additional segment of 279 nucleotides in the 3′-untranslated region. The two mRNA seemed to arise by the use of an alternate polyadenylation site of the same primary transcript. Ribonuclease protection assays revealed that the concentrations of the longer mRNA in the normal hippocampus and the hippocampus of patients with AD brains were similar.