DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced neurotoxicity in rats

Brain Res Bull. 2012 Sep 1;88(6):609-16. doi: 10.1016/j.brainresbull.2012.05.013. Epub 2012 Jun 1.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / therapeutic use*
  • Apomorphine / antagonists & inhibitors
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Dopamine / analysis
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / enzymology
  • Drug Evaluation, Preclinical
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Intracellular Signaling Peptides and Proteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins / therapeutic use*
  • Ion Channels / biosynthesis
  • Ion Channels / genetics
  • Leupeptins / toxicity*
  • Male
  • Microinjections
  • Mitochondrial Membrane Transport Proteins / biosynthesis
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / genetics
  • Mitochondrial Uncoupling Proteins
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Oncogene Proteins / administration & dosage
  • Oncogene Proteins / therapeutic use*
  • Oxidative Stress / drug effects
  • Oxidopamine / toxicity*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / prevention & control*
  • Protein Deglycase DJ-1
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Superoxide Dismutase / biosynthesis
  • Superoxide Dismutase / genetics
  • Tyrosine 3-Monooxygenase / analysis
  • alpha-Synuclein / biosynthesis
  • alpha-Synuclein / genetics

Substances

  • Antiparkinson Agents
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intracellular Signaling Peptides and Proteins
  • Ion Channels
  • Leupeptins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Mitochondrial Uncoupling Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Oncogene Proteins
  • Slc25a14 protein, rat
  • Slc25a27 protein, rat
  • alpha-Synuclein
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Apomorphine
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • Dopamine