Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway
10.4062/biomolther.2020.154
- Author:
Eun Ji YEO
1
;
Won Sik EUM
;
Hyeon Ji YEO
;
Yeon Joo CHOI
;
Eun Jeong SOHN
;
Hyun Jung KWON
;
Dae Won KIM
;
Duk-Soo KIM
;
Sung-Woo CHO
;
Jinseu PARK
;
Kyu Hyung HAN
;
Keun Wook LEE
;
Jong Kook PARK
;
Min Jea SHIN
;
Soo Young CHOI
Author Information
1. Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2021;29(3):321-330
- CountryRepublic of Korea
- Language:English
-
Abstract:
Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.
