Abstract
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a doseand time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Animals
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Blood-Brain Barrier / metabolism
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Brain Ischemia / metabolism*
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Brain Ischemia / pathology
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Brain Ischemia / prevention & control
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CA1 Region, Hippocampal / drug effects
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CA1 Region, Hippocampal / metabolism
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CA1 Region, Hippocampal / pathology
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Cell Line, Tumor
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Cell Survival / drug effects
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Gerbillinae
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Intracellular Signaling Peptides and Proteins / administration & dosage*
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Intracellular Signaling Peptides and Proteins / biosynthesis
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Intracellular Signaling Peptides and Proteins / pharmacokinetics
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Lipid Peroxidation
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Malondialdehyde / metabolism
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Mice
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Neuroprotective Agents / administration & dosage*
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Neuroprotective Agents / pharmacokinetics
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Oncogene Proteins / administration & dosage*
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Oncogene Proteins / biosynthesis
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Oncogene Proteins / pharmacokinetics
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Oxidative Stress*
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Prosencephalon / drug effects
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Prosencephalon / metabolism
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Prosencephalon / pathology
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Protein Deglycase DJ-1
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Rats
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Recombinant Fusion Proteins / administration & dosage*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / pharmacokinetics
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tat Gene Products, Human Immunodeficiency Virus / administration & dosage*
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tat Gene Products, Human Immunodeficiency Virus / biosynthesis
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tat Gene Products, Human Immunodeficiency Virus / pharmacokinetics
Substances
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Intracellular Signaling Peptides and Proteins
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Neuroprotective Agents
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Oncogene Proteins
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Recombinant Fusion Proteins
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tat Gene Products, Human Immunodeficiency Virus
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Malondialdehyde
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PARK7 protein, human
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Protein Deglycase DJ-1