Expression and Localization of Mitochondrial Ferritin mRNA in Alzheimer's Disease Cerebral Cortex
Open Access
- 20 July 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (7), e22325
- https://doi.org/10.1371/journal.pone.0022325
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 H2O2 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.This publication has 43 references indexed in Scilit:
- Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's DiseaseCell, 2010
- Deposition of lactoferrin in fibrillar-type senile plaques in the brains of transgenic mouse models of Alzheimer's diseaseNeuroscience Letters, 2010
- Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examplesArchives of Toxicology, 2010
- Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosolProceedings of the National Academy of Sciences of the United States of America, 2010
- Mitochondrial Ferritin in the Substantia Nigra in Restless Legs SyndromeJournal of Neuropathology and Experimental Neurology, 2009
- Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's diseaseNeuroscience Letters, 2009
- Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxiaHuman Molecular Genetics, 2008
- The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007Cell and Tissue Banking, 2008
- Iron: The Redox-active Center of Oxidative Stress in Alzheimer DiseaseNeurochemical Research, 2007
- Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's diseaseJournal of Neurochemistry, 2002