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KMID : 0606920210290030321
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Biomolecules & Therapeutics
2021 Volume.29 No. 3 p.321 ~ p.330
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Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway
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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 Jin-Seu
Han Kyu-Hyung
Lee Keun-Wook
Park Jong-Kook
Shin Min-Jea
Choi Soo-Young
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Abstract
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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 H2O2-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.
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KEYWORD
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Tat-Trx1, ASK1, ROS, Apoptosis, Ischemia, Protein therapy
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