Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex

• Published in: PloS one 2011-07, Vol.6 (7), p.e22325
• Main Authors: Wang, Ligang, Yang, Hongkuan, Zhao, Shiguang, Sato, Haruhisa, Konishi, Yoshihiro, Beach, Thomas G, Abdelalim, Essam Mohamed, Bisem, Naomi J, Tooyama, Ikuo
• Format: Article
• Language: English
• Subjects: Advertising executives; Age; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Apoptosis; Ataxia; Blotting, Western; Brain; Brain research; Case-Control Studies; Cell culture; Cell Death - drug effects; Cell Line, Tumor; Cerebral cortex; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Chromosome 5; Ferritin; Friedreich's ataxia; Gene expression; Gene Expression Regulation - drug effects; Glial cells; Histochemistry; Homeostasis; Hospitals; Humans; Hybridization; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Hypotheses; In Situ Hybridization; In vitro methods and tests; Iron; Kinases; Localization; Medicine; Messenger RNA; Metabolism; Mitochondria; mRNA; Nervous system; Neuroblastoma; Neurodegenerative diseases; Neuronal-glial interactions; Neuroprotection; Neurosciences; Neurosurgery; Oxidative stress; Oxidative Stress - drug effects; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptides; Polymerase chain reaction; Protein Multimerization - drug effects; Protein Structure, Secondary; Protein Transport - drug effects; Proteins; Real time; Real-Time Polymerase Chain Reaction; Restless legs syndrome; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Science; Vaccines; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022325

Mitochondrial ferritin (MtF) has been identified as a novel ferritin encoded by an intron-lacking gene with specific mitochondrial localization located on chromosome 5q23.1. MtF has been associated with neurodegenerative disorders such as Friedreich ataxia and restless leg syndrome. However, little information is available about MtF in Alzheimer's disease (AD). In this study, therefore, we investigated the expression and localization of MtF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) as well as in situ hybridization histochemistry. We also examined protein expression using western-blot assay. In addition, we used in vitro methods to further explore the effect of oxidative stress and β-amyloid peptide (Aβ) on MtF expression. To do this we examined MtF mRNA and protein expression changes in the human neuroblastoma cell line, IMR-32, after treatment with Aβ, H2O2, or both. The neuroprotective effect of MtF on oxidative stress induced by H(2)O(2) was measured by MTT assay. The in situ hybridization studies revealed that MtF mRNA was detected mainly in neurons to a lesser degree in glial cells in the cerebral cortex. The staining intensity and the number of positive cells were increased in the cerebral cortex of AD patients. Real-time PCR and western-blot confirmed that MtF expression levels in the cerebral cortex were significantly higher in AD cases than that in control cases at both the mRNA and the protein level. Cell culture experiments demonstrated that the expression of both MtF mRNA and protein were increased by treatment with H2O2 or a combination of Aβ and H2O2, but not with Aβ alone. Finally, MtF expression showed a significant neuroprotective effect against H2O2-induced oxidative stress (p