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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
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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