Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

• Published in: Biomolecules & therapeutics Vol. 29; no. 3; pp. 321 - 330
• Main Authors: Yeo, Eun Ji, Eum, Won Sik, Yeo, Hyeon Ji, Choi, Yeon Joo, Sohn, Eun Jeong, Kwon, Hyun Jung, Kim, Dae Won, Kim, Duk-Soo, Cho, Sung-Woo, Park, Jinseu, Han, Kyu Hyung, Lee, Keun Wook, Park, Jong Kook, Shin, Min Jea, Choi, Soo Young
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.05.2021; 한국응용약물학회
• Subjects: Original; 약학; Ischemia; ASK1; Protein therapy; Tat-Trx1; ROS; Apoptosis
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2020.154

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 O -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.