Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway
| Autor: | Yeon Joo Choi, Jinseu Park, Dae Won Kim, Hyeon Ji Yeo, Eun Jeong Sohn, Sung-Woo Cho, Jong Kook Park, Kyu Hyung Han, Duk-Soo Kim, Soo Young Choi, Keun Wook Lee, Hyun Jung Kwon, Won Sik Eum, Eun Ji Yeo, Min Jea Shin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Programmed cell death Tat-Trx1 Cell Apoptosis Protein therapy Biochemistry 03 medical and health sciences 0302 clinical medicine Ischemia Drug Discovery medicine Protein kinase B Pharmacology Microglia Chemistry ROS Cell biology ASK1 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Molecular Medicine Original Article Signal transduction Intracellular |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 2005-4483 1976-9148 |
| DOI: | 10.4062/biomolther.2020.154 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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