Format

Send to

Choose Destination
Exp Neurobiol. 2019 Oct 31;28(5):612-627. doi: 10.5607/en.2019.28.5.612.

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

Author information

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

Abstract

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.

KEYWORDS:

Cytotoxicity; Ischemia; MAPKs; Oxidative stress; Protein therapy; Tat-AR

Supplemental Content

Full text links

Icon for The Korean Society for Brain and Neural Science Icon for PubMed Central
Loading ...
Support Center