ArticlePloS one2013
Mechanisms of Nrf2 protection in astrocytes as identified by quantitative proteomics and siRNA screening.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Glutathione Metabolism of the Brain-The Role of Astrocytes.Journal of neurochemistry · 2025Review
- Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.Neurochemical research · 2024Article
- Inhibiting the Keap1/Nrf2 Protein-Protein Interaction with Protein-Like Polymers.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- The human PTGR1 gene expression is controlled by TE-derived Z-DNA forming sequence cooperating with miR-6867-5p.Scientific reports · 2024Article
- A pure compound fromHeliyon · 2022Article
- Sp1-Mediated Prdx6 Upregulation Leads to Clasmatodendrosis by Increasing Its aiPLA2 Activity in the CA1 Astrocytes in Chronic Epilepsy Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Revisiting Astrocytic Roles in Methylmercury Intoxication.Molecular neurobiology · 2021Review
- KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke.Journal of neuroinflammation · 2020Article
- Skeletal muscle proteome analysis provides insights on high altitude adaptation of yaks.Molecular biology reports · 2019Article
- Galanin Protects Rat Cortical Astrocyte from Oxidative Stress: Involvement of GalR2 and pERK1/2 Signal Pathway.Mediators of inflammation · 2019Article
- Astrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion.Scientific reports · 2018Article
- Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes.Antioxidants (Basel, Switzerland) · 2017Review
- Article
- High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress.Stem cells translational medicine · 2016Article
- Glutathione-Dependent Detoxification Processes in Astrocytes.Neurochemical research · 2015Review
- Article
- Temporal and spatial dynamics of nrf2-antioxidant response elements mediated gene targets in cortex and hippocampus after controlled cortical impact traumatic brain injury in mice.Journal of neurotrauma · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Nrf2 (NF-E2 related factor 2)-ARE (antioxidant response element) pathway controls a powerful array of endogenous cellular antioxidant systems and is an important pathway in the detoxification of reactive oxygen species (ROS) in the brain. Using a combination of quantitative proteomics and siRNA screening, we have identified novel protective mechanisms of the Nrf2-ARE pathway against oxidative stress in astrocytes. Studies from our lab and others have shown Nrf2 overexpression protects astrocytes from oxidative stress. However, the exact mechanisms by which Nrf2 elicits these effects are unknown. In this study, we show that induction of Nrf2 reduces levels of reactive oxygen species (ROS) produced by various oxidative stressors and results in robust cytoprotection. To identify the enzymes responsible for these effects, we used stable isotope labeling by amino acids in cell culture (SILAC) and quantitative shotgun proteomics to identify 72 Nrf2-regulated proteins in astrocytes. We hypothesized a subset of these proteins might play a critical role in Nrf2 protection. In order to identify these critical proteins, we used bioinformatics to narrow our target list of proteins and then systematically screened each candidate with siRNA to assess the role of each in Nrf2 protection. We screened each target against H2O2, tert-butyl hydroperoxide, and 4-hydroxynonenal and subsequently identified three enzymes-catalase, prostaglandin reductase-1, and peroxiredoxin-6-that are critical for Nrf2-mediated protection in astrocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.