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Title: Coenzyme Q<inf>10</inf>provides neuroprotection in iron-induced apoptosis in dopaminergic neurons
Authors: Patcharee Kooncumchoo
Sushil Sharma
James Porter
Piyarat Govitrapong
Manuchir Ebadi
University of North Dakota School of Medicine &amp; Health Sciences
Mahidol University
Keywords: Neuroscience
Issue Date: 31-May-2006
Citation: Journal of Molecular Neuroscience. Vol.28, No.2 (2006), 125-142
Abstract: The exact molecular mechanism of progressive loss of neuromelanin containing nigrostriatal dopaminergic neurons in Parkinson's disease (PD) remains unknown, yet evidence suggests that iron might play an important role in PD pathology. In this study we have determined the neuroprotective role of coenzyme Q10(CoQ10) in iron-induced apoptosis in cultured human dopaminergic (SK-N-SH) neurons, in metallothionein gene-manipulated mice, and in α-synuclein knockout (α-synko) mice with a primary objective to assess a possible therapeutic and anti-inflammatory potential for CoQ10in PD. Iron-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species production, increased metallothionein and glutathione synthesis, caspase-3 activation, NF-κB induction, and decreased Bcl-2 expression, without any significant change in Bax expression. Lower concentrations of FeSO4(1-10 μM) induced perinuclear aggregation of mitochondria, whereas higher concentrations (100-250 μM) induced CoQ10depletion, plasma membrane perforations, mitochondrial damage, and nuclear DNA condensation and fragmentation. FeSO4-induced deleterious changes were attenuated by pre-treatment with CoQ10and by deferoxamine, a potent iron chelator, in SK-N-SH cells. 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP)-induced striatal release of free iron, and NF-κB expression were significantly increased; whereas ferritin and melanin synthesis were significantly reduced in the substantia nigra pars compacta (SNpc) of MTdkomice as compared with controlwtmice, MTtransmice, and α-synko mice. CoQ10treatment inhibited MPTP-induced NF-κB induction in all of the genotypes. These data suggest that glutathione and metallothionein synthesis might be induced as an attempt to combat iron-induced oxidative stress, whereas exogenous administration of CoQ10or of metallothionein induction might provide CoQ10-mediated neuroprotection in PD. Copyright © 2006 Humana Press Inc. All rights of any nature whatsoever are reserved.
ISSN: 08958696
Appears in Collections:Scopus 2006-2010

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