DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced neurotoxicity in rats.
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.
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
Shuang-Yong
SY
Sun
Chun-Na
CN
An
Xiao-Ping
XP
Pu
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001058:Apomorphine / Q000037:antagonists & inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000032:analysis; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics; D007976:Leupeptins / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D033681:Mitochondrial Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D000071245:Mitochondrial Uncoupling Proteins; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015513:Oncogene Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000978:Antiparkinson Agents; D001058:Apomorphine; D004298:Dopamine; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D007976:Leupeptins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D016627:Oxidopamine; D000071617:Protein Deglycase DJ-1; D013482:Superoxide Dismutase; D014446:Tyrosine 3-Monooxygenase; D051844:alpha-Synuclein; D000099156:Superoxide Dismutase 2; C497444:Hif1a protein, rat; C492125:Slc25a14 protein, rat; C494853:Slc25a27 protein, rat; C105131:PARK7 protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde