Peroxiredoxin 4 ameliorates amyloid beta oligomer-mediated apoptosis by inhibiting ER-stress in HT-22 hippocampal neuron cells
| Autor: | Bokyung Kim, Sang-Rae Lee, Yong Chul Bae, Dong-Seok Lee, Dong Gil Lee, Min Kyoung Kam, Hyun-Shik Lee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Amyloid beta Health Toxicology and Mutagenesis Apoptosis Toxicology medicine.disease_cause Cell Line Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Neurons Amyloid beta-Peptides Cell Death biology Chemistry Endoplasmic reticulum Hydrogen Peroxide Peroxiredoxins Cell Biology Endoplasmic Reticulum Stress Mitochondria Cell biology Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Unfolded protein response Calcium Reactive Oxygen Species Intracellular Oxidative stress Signal Transduction |
| Zdroj: | Cell Biology and Toxicology. 35:573-588 |
| ISSN: | 1573-6822 0742-2091 |
| DOI: | 10.1007/s10565-019-09477-5 |
| Popis: | Alzheimer's disease (AD) is a neurodegenerative disorder caused by amyloid beta oligomers (AβO), which induce cell death by triggering oxidative stress and endoplasmic reticulum (ER) stress. Oxidative stress is regulated by antioxidant enzymes, including peroxiredoxins. Peroxiredoxins (Prx) are classified into six subtypes, based on their localization and cysteine residues, and protect cells by scavenging hydrogen peroxide (H2O2). Peroxiredoxin 4 (Prx4) is unique in being localized to the ER; however, whether Prx4 protects neuronal cells from AβO-induced toxicity remains unclear, although Prx4 expression is upregulated in AβO-induced oxidative stress and ER stress. In this study, we established HT-22 cells in which Prx4 was either overexpressed or silenced to investigate its role in AβO-induced toxicity. AβO-stimulation of HT-22 cells with overexpressed Prx4 caused decreases in both AβO-induced ROS and ER stress (followed by ER expansion). In contrast, AβO stimulation caused increases in both ROS and ER stress that were notably higher in HT-22 cells with silenced Prx4 expression than in HT-22 cells. Consequently, Prx4 overexpression decreased apoptotic cell death and ameliorated the AβO-induced increase in intracellular Ca2+. Therefore, we conclude that Prx4 has a protective effect against AβO-mediated oxidative stress, ER stress, and neuronal cell death. Furthermore, these results suggest that Prx4 may be a target for preventing AβO toxicity in AD. Graphical abstract . |
| Databáze: | OpenAIRE |
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