Downregulation of TRIM8 protects neurons from oxygen-glucose deprivation/re-oxygenation-induced injury through reinforcement of the AMPK/Nrf2/ARE antioxidant signaling pathway
| Autor: | Wei Zhao, Yan Feng, Yan Chen, Xiajing Zhang, Yongping Shao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
NF-E2-Related Factor 2 Ubiquitin-Protein Ligases Apoptosis Nerve Tissue Proteins medicine.disease_cause Neuroprotection 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation medicine Animals Protein kinase A Molecular Biology chemistry.chemical_classification Neurons Reactive oxygen species General Neuroscience Adenylate Kinase AMPK medicine.disease Cell biology Oxygen Oxidative Stress 030104 developmental biology Glucose nervous system chemistry Reperfusion Injury Neurology (clinical) Signal transduction Reactive Oxygen Species Reperfusion injury 030217 neurology & neurosurgery Oxidative stress Developmental Biology Signal Transduction |
| Zdroj: | Brain research. 1728 |
| ISSN: | 1872-6240 |
| Popis: | Tripartite motif 8 (TRIM8) has emerged as a crucial regulator of cell survival, apoptosis, and oxidative stress in various pathological processes. However, TRIM8's involvement in regulating neuronal injury in cerebral ischemia/reperfusion injury remains largely uncharacterized. In the present study, we aimed to investigate the potential function and molecular mechanism of TRIM8 in regulating neuronal apoptosis and oxidative stress induced by oxygen-glucose deprivation/re-oxygenation (OGD/R) in an in vitro model to study cerebral ischemia/reperfusion injury. Herein, we found that TRIM8 expression was upregulated in neurons exposed to OGD/R. Knockdown of TRIM8 improved the viability and decreased the apoptosis and reactive oxygen species (ROS) generation in OGD/R-exposed neurons, whereas TRIM8 overexpression showed the opposite effect. Notably, TRIM8 inhibition increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Moreover, TRIM8 inhibition promoted the transcriptional activity of the Nrf2/antioxidant response element (ARE). However, AMPK inhibition partially reversed TRIM8 downregulation-mediated Nrf2/ARE activation and the neuroprotective effect in OGD/R-exposed neurons. Additionally, silencing of Nrf2 also markedly abrogated TRIM8 downregulation-mediated neuroprotection. Overall, these results demonstrate that downregulation of TRIM8 protects from OGD/R-induced neuronal injury by reinforcing the activation of Nrf2/ARE antioxidant signaling via AMPK, suggesting a potential role for TRIM8 in cerebral ischemia/reperfusion injury. |
| Databáze: | OpenAIRE |
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