title: Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex.
abstract: 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<0.05). The present study suggests that MtF is involved in the pathology of AD and may play a neuroprotective role against oxidative stress.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Ligang
authors.initials: L
authors.lastname: Wang
authors.forename: Hongkuan
authors.initials: H
authors.lastname: Yang
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Sato
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Konishi
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Essam Mohamed
authors.initials: EM
authors.lastname: Abdelalim
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Bisem
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017403:In Situ Hybridization; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D006861:Hydrogen Peroxide