Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine- induced dopaminergic cell damage: Implication for neuroprotection in parkinson's disease

Zhen Hua Shi, Guangjun Nie, Xiang Lin Duan, Tracey Rouault, Wen Shuang Wu, Bo Ning, Nan Zhang, Yan Zhong Chang, Bao Lu Zhao

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Neuronal iron homeostasis disruption and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Adult iron-regulatory protein 2 knockout (Ireb2-/-) mice develop iron accumulation in white matter tracts and nuclei in different brain area and display severe neurodegeneration in Purkinje cells of the cerebrum. Mitochondrial ferritin (MtFt), a newly discovered ferritin, specifically expresses in high energy-consuming cells, including neurons of brain and spinal cord. Interestingly, the decreased expression of MtFt in cerebrum, but not in striatum, matches the differential neurodegeneration pattern in these Ireb2 -/- mice. To explore its effect on neurodegeneration, the effects of MtFt expression on 6-hydrodopamine (6-OHDA)-induced neuronal damage was examined. The overexpression of MtFt led to a cytosolic iron deficiency in the neuronal cells and significantly prevented the alteration of iron redistribution induced by 6-OHDA. Importantly, MtFt strongly inhibited mitochondrial damage, decreased production of the reactive oxygen species and lipid peroxidation, and dramatically rescued apoptosis by regulating Bcl-2, Bax and caspase-3 pathways. In conclusion, this study demonstrates that MtFt plays an important role in preventing neuronal damage in an 6-OHDA-induced parkinsonian phenotype by maintaining iron homeostasis. Regulation of MtFt expression in neuronal cells may provide a new neuroprotective strategy for PD. Antioxid.

Original languageEnglish (US)
Pages (from-to)783-796
Number of pages14
JournalAntioxidants and Redox Signaling
Volume13
Issue number6
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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