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

Ligang Wang, Hongkuan Yang, Shiguang Zhao, Haruhisa Sato, Yoshihiro Konishi, Thomas G. Beach, Essam Mohamed, Naomi J. Bisem, Ikuo Tooyama

Research output: Contribution to journalArticle

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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 2O 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.

Original languageEnglish
Article numbere22325
JournalPLoS One
Volume6
Issue number7
DOIs
Publication statusPublished - 26 Jul 2011
Externally publishedYes

Fingerprint

cerebral cortex
ferritin
Alzheimer disease
Ferritins
messenger RNA
Cerebral Cortex
Alzheimer Disease
Messenger RNA
Oxidative stress
Oxidative Stress
oxidative stress
neuroprotective effect
Polymerase chain reaction
Neuroprotective Agents
mitochondrial messenger RNA
in situ hybridization
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Assays
quantitative polymerase chain reaction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wang, L., Yang, H., Zhao, S., Sato, H., Konishi, Y., Beach, T. G., ... Tooyama, I. (2011). Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex. PLoS One, 6(7), [e22325]. https://doi.org/10.1371/journal.pone.0022325

Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex. / Wang, Ligang; Yang, Hongkuan; Zhao, Shiguang; Sato, Haruhisa; Konishi, Yoshihiro; Beach, Thomas G.; Mohamed, Essam; Bisem, Naomi J.; Tooyama, Ikuo.

In: PLoS One, Vol. 6, No. 7, e22325, 26.07.2011.

Research output: Contribution to journalArticle

Wang, L, Yang, H, Zhao, S, Sato, H, Konishi, Y, Beach, TG, Mohamed, E, Bisem, NJ & Tooyama, I 2011, 'Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex', PLoS One, vol. 6, no. 7, e22325. https://doi.org/10.1371/journal.pone.0022325
Wang, Ligang ; Yang, Hongkuan ; Zhao, Shiguang ; Sato, Haruhisa ; Konishi, Yoshihiro ; Beach, Thomas G. ; Mohamed, Essam ; Bisem, Naomi J. ; Tooyama, Ikuo. / Expression and localization of mitochondrial ferritin mRNA in Alzheimer's disease cerebral cortex. In: PLoS One. 2011 ; Vol. 6, No. 7.
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