Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.

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.

• Authors: Hoon Jae Jeong, Dae Won Kim, Mi Jin Kim, Su Jung Woo, Hye Ri Kim, So Mi Kim, Hyo Sang Jo, Hyun Sook Hwang, Duk Soo Kim, Sung Woo Cho, Moo Ho Won, Kyu Hyung Han, Jin Seu Park, Won Sik Eum, Soo Young Choi
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 44 Issue 10 Pg. 586-93 (Oct 31 2012) ISSN: 2092-6413 [Electronic] United States
• PMID: 22847454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Neuroprotective Agents
• Oncogene Proteins
• Recombinant Fusion Proteins
• tat Gene Products, Human Immunodeficiency Virus
• Malondialdehyde
• PARK7 protein, human
• Protein Deglycase DJ-1

Topics

• 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)
• Protein Deglycase DJ-1
• Rats
• Recombinant Fusion Proteins (administration & dosage, biosynthesis, pharmacokinetics)
• tat Gene Products, Human Immunodeficiency Virus (administration & dosage, biosynthesis, pharmacokinetics)