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Mol. Cells 2012; 33(5): 471-478

Published online May 31, 2012

https://doi.org/10.1007/s10059-012-2255-8

© The Korean Society for Molecular and Cellular Biology

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

Hoon Jae Jeong1,5, Dae Won Kim1,5, Su Jung Woo1, Hye Ri Kim1, So Mi Kim1, Hyo Sang Jo1, Meeyoung Park1, Duk-Soo Kim2, Oh-Shin Kwon3, In Koo Hwang4, Kyu Hyung Han1, Jinseu Park1, Won Sik Eum1,*, and Soo Young Choi1,*

1Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea, 2Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea, 3School of Life Science and Biotechnology, Kyungbook National University, Daegu 702-701, Korea, 4Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Korea, 5These authors equally contributed to this work.

Correspondence to : *Correspondence: sychoi@hallym.ac.kr (SYC); wseum@hallym.ac.kr (WSE)

Received: November 14, 2011; Revised: March 1, 2012; Accepted: March 2, 2012

Abstract

Parkinson’s disease (PD) is a well known neurodegenera-tive disorder characterized by selective loss of dopamin-ergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD.

Keywords antioxidant, Parkinson disease, protein transduction, ROS, Tat-DJ-1

Article

Research Article

Mol. Cells 2012; 33(5): 471-478

Published online May 31, 2012 https://doi.org/10.1007/s10059-012-2255-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

Hoon Jae Jeong1,5, Dae Won Kim1,5, Su Jung Woo1, Hye Ri Kim1, So Mi Kim1, Hyo Sang Jo1, Meeyoung Park1, Duk-Soo Kim2, Oh-Shin Kwon3, In Koo Hwang4, Kyu Hyung Han1, Jinseu Park1, Won Sik Eum1,*, and Soo Young Choi1,*

1Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea, 2Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea, 3School of Life Science and Biotechnology, Kyungbook National University, Daegu 702-701, Korea, 4Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Korea, 5These authors equally contributed to this work.

Correspondence to:*Correspondence: sychoi@hallym.ac.kr (SYC); wseum@hallym.ac.kr (WSE)

Received: November 14, 2011; Revised: March 1, 2012; Accepted: March 2, 2012

Abstract

Parkinson’s disease (PD) is a well known neurodegenera-tive disorder characterized by selective loss of dopamin-ergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD.

Keywords: antioxidant, Parkinson disease, protein transduction, ROS, Tat-DJ-1

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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