Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.
- Author:
Hoon Jae JEONG
1
;
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
;
Jinseu PARK
;
Won Sik EUM
;
Soo Young CHOI
Author Information
1. Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. sychoi@hallym.ac.kr
- Publication Type:Retracted Publication ; Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
brain ischemia;
CA1 region, hippocampal;
cell survival;
neurons;
PARK7 protein, human;
reactive oxygen species;
toxicity
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(10):586-593
- CountryRepublic of Korea
- Language:English
-
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.
