Exp Mol Med.
2012 Oct;44(10):586-593.
Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury
- Affiliations
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- 1Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. sychoi@hallym.ac.kr
- 2Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
- 3Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
- 4Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
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 dose- and 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.
Keyword
MeSH Terms
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Animals
Blood-Brain Barrier/metabolism
Brain Ischemia/*metabolism/pathology/prevention & control
CA1 Region, Hippocampal/drug effects/metabolism/pathology
Cell Line, Tumor
Cell Survival/drug effects
Gerbillinae
Intracellular Signaling Peptides and Proteins/*administration & dosage/biosynthesis/pharmacokinetics
Lipid Peroxidation
Malondialdehyde/metabolism
Mice
Neuroprotective Agents/*administration & dosage/pharmacokinetics
Oncogene Proteins/*administration & dosage/biosynthesis/pharmacokinetics
*Oxidative Stress
Prosencephalon/drug effects/metabolism/pathology
Rats
Recombinant Fusion Proteins/*administration & dosage/biosynthesis/pharmacokinetics
tat Gene Products, Human Immunodeficiency Virus/*administration & dosage/biosynthesis/pharmacokinetics
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