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

54 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Oxidopamine
Ferritins
Parkinson Disease
Cells
Iron
Cerebrum
Iron Regulatory Protein 2
Brain
Homeostasis
Oxidative stress
Neuroprotection
Purkinje Cells
Knockout Mice
Caspase 3
Lipid Peroxidation
Neurons
Reactive Oxygen Species
Spinal Cord
Oxidative Stress
Apoptosis

ASJC Scopus subject areas

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

Cite this

Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine- induced dopaminergic cell damage : Implication for neuroprotection in parkinson's disease. / Shi, Zhen Hua; Nie, Guangjun; Duan, Xiang Lin; Rouault, Tracey; Wu, Wen Shuang; Ning, Bo; Zhang, Nan; Chang, Yan Zhong; Zhao, Bao Lu.

In: Antioxidants and Redox Signaling, Vol. 13, No. 6, 15.09.2010, p. 783-796.

Research output: Contribution to journalArticle

Shi, Zhen Hua ; Nie, Guangjun ; Duan, Xiang Lin ; Rouault, Tracey ; Wu, Wen Shuang ; Ning, Bo ; Zhang, Nan ; Chang, Yan Zhong ; Zhao, Bao Lu. / Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine- induced dopaminergic cell damage : Implication for neuroprotection in parkinson's disease. In: Antioxidants and Redox Signaling. 2010 ; Vol. 13, No. 6. pp. 783-796.
@article{7d509f06338d43ab9521bb160249ea01,
title = "Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine- induced dopaminergic cell damage: Implication for neuroprotection in parkinson's disease",
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.",
author = "Shi, {Zhen Hua} and Guangjun Nie and Duan, {Xiang Lin} and Tracey Rouault and Wu, {Wen Shuang} and Bo Ning and Nan Zhang and Chang, {Yan Zhong} and Zhao, {Bao Lu}",
year = "2010",
month = "9",
day = "15",
doi = "10.1089/ars.2009.3018",
language = "English (US)",
volume = "13",
pages = "783--796",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine- induced dopaminergic cell damage

T2 - Implication for neuroprotection in parkinson's disease

AU - Shi, Zhen Hua

AU - Nie, Guangjun

AU - Duan, Xiang Lin

AU - Rouault, Tracey

AU - Wu, Wen Shuang

AU - Ning, Bo

AU - Zhang, Nan

AU - Chang, Yan Zhong

AU - Zhao, Bao Lu

PY - 2010/9/15

Y1 - 2010/9/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77954929704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954929704&partnerID=8YFLogxK

U2 - 10.1089/ars.2009.3018

DO - 10.1089/ars.2009.3018

M3 - Article

C2 - 20121342

AN - SCOPUS:77954929704

VL - 13

SP - 783

EP - 796

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 6

ER -