Abstract
Parkinson disease (PD) is the second most common neurodegenerative disease, and it cannot be completely cured by current medications. In this study, DJ-1 protein was administrated into medial forebrain bundle of PD model rats those had been microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1 protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine contents and tyrosine hydroxylase levels in the striatum, and decrease dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats, uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA and SOD2 protein were increased when DJ-1 protein was co-injected. Simultaneously, administration of DJ-1 protein reduced α-synuclein and hypoxia-inducible factor 1α mRNA and α-synuclein protein in MG-132 lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD model rats by increasing antioxidant capacity and inhibiting α-synuclein expression.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiparkinson Agents / administration & dosage
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Antiparkinson Agents / therapeutic use*
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Apomorphine / antagonists & inhibitors
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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Corpus Striatum / pathology
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Dopamine / analysis
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Dopaminergic Neurons / drug effects*
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Dopaminergic Neurons / enzymology
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Drug Evaluation, Preclinical
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Intracellular Signaling Peptides and Proteins / administration & dosage
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Intracellular Signaling Peptides and Proteins / therapeutic use*
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Ion Channels / biosynthesis
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Ion Channels / genetics
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Leupeptins / toxicity*
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Male
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Microinjections
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Mitochondrial Membrane Transport Proteins / biosynthesis
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Proteins / biosynthesis
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Mitochondrial Proteins / genetics
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Mitochondrial Uncoupling Proteins
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Motor Activity / drug effects
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / therapeutic use*
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Oncogene Proteins / administration & dosage
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Oncogene Proteins / therapeutic use*
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Oxidative Stress / drug effects
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Oxidopamine / toxicity*
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Parkinsonian Disorders / chemically induced
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Parkinsonian Disorders / drug therapy
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Parkinsonian Disorders / prevention & control*
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Protein Deglycase DJ-1
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Rats
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Rats, Sprague-Dawley
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism
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Substantia Nigra / pathology
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Superoxide Dismutase / biosynthesis
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Superoxide Dismutase / genetics
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Tyrosine 3-Monooxygenase / analysis
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alpha-Synuclein / biosynthesis
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alpha-Synuclein / genetics
Substances
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Antiparkinson Agents
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Hif1a protein, rat
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Hypoxia-Inducible Factor 1, alpha Subunit
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Intracellular Signaling Peptides and Proteins
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Ion Channels
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Leupeptins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Proteins
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Mitochondrial Uncoupling Proteins
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Nerve Tissue Proteins
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Neuroprotective Agents
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Oncogene Proteins
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Slc25a14 protein, rat
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Slc25a27 protein, rat
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alpha-Synuclein
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Oxidopamine
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Tyrosine 3-Monooxygenase
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Superoxide Dismutase
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superoxide dismutase 2
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PARK7 protein, human
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Protein Deglycase DJ-1
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Apomorphine
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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Dopamine