Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage
- Author:
Su Bin CHO
1
;
Won Sik EUM
;
Min Jea SHIN
;
Hyun Jung KWON
;
Jung Hwan PARK
;
Yeon Joo CHOI
;
Jinseu PARK
;
Kyu Hyung HAN
;
Ju Hyeon KANG
;
Duk Soo KIM
;
Sung Woo CHO
;
Dae Won KIM
;
Soo Young CHOI
Author Information
- Publication Type:Original Article
- Keywords: Tat-AR; Oxidative stress; Ischemia; MAPKs; Cytotoxicity; Protein therapy
- MeSH: Aldehyde Reductase; Aldehydes; Blood-Brain Barrier; Brain; CA1 Region, Hippocampal; Caspase 3; Cell Death; Cell Survival; Humans; In Vitro Techniques; Ischemia; Models, Animal; Neurons; Oxidative Stress; Oxidoreductases; Protein Kinases
- From:Experimental Neurobiology 2019;28(5):612-627
- CountryRepublic of Korea
- Language:English
- 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.
