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  • the Korean Society for Brain and Neural Sciences

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Original Article

Exp Neurobiol 2019; 28(5): 612-627

Published online October 31, 2019

https://doi.org/10.5607/en.2019.28.5.612

© The Korean Society for Brain and Neural Sciences

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Su Bin Cho1†, Won Sik Eum1†, Min Jea Shin1†, Hyun Jung Kwon2, Jung Hwan Park1, Yeon Joo Choi1, Jinseu Park1, Kyu Hyung Han1, Ju Hyeon Kang3, Duk-Soo Kim3, Sung-Woo Cho4, Dae Won Kim2* and Soo Young Choi1*

1Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, 2Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, 3Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 31538, 4Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Korea

Correspondence to: *To whom correspondence should be addressed.
Soo Young Choi, TEL: 82-33-248-2112, FAX: 82-33-248-3202
e-mail: sychoi@hallym.ac.kr
Dae Won Kim, TEL: 82-33-640-2229, FAX: 82-33-642-6410
e-mail: kimdw@gwnu.ac.kr
These authors contributed equally to this work.

Received: March 25, 2019; Revised: August 6, 2019; Accepted: September 2, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, andreproduction in any medium, provided the original work is properly cited.

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Graphical Abstract


Keywords: Tat-AR, Oxidative stress, Ischemia, MAPKs, Cytotoxicity, Protein therapy