ArticleAging cell2012
Identification of age-specific Nrf2 binding to a novel antioxidant response element locus in the Gclc promoter: a compensatory means for the loss of glutathione synthetic capacity in the aging rat liver?
Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.Life medicine · 2024Article
- Aging of Liver in Its Different Diseases.International journal of molecular sciences · 2022Review
- Article
- The Effect of Acute Aerobic Exercise on Redox Homeostasis and Mitochondrial Function of Rat White Adipose Tissue.Oxidative medicine and cellular longevity · 2021Article
- Understanding the Relationship between Glutathione, TGF-β, and Vitamin D in CombatingJournal of clinical medicine · 2020Review
- Attenuation of Age-Related Hepatic Steatosis byAdvances in pharmacological and pharmaceutical sciences · 2020Article
- Article
- Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles ('vehicular smog').Free radical biology & medicine · 2018Article
- Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress.Scientific reports · 2017Article
- Identification of miR-31-5p, miR-141-3p, miR-200c-3p, and GLT1 as human liver aging markers sensitive to donor-recipient age-mismatch in transplants.Aging cell · 2017Article
- Nrf2 mediates redox adaptations to exercise.Redox biology · 2016Review
- The status of Nrf2-based therapeutics: current perspectives and future prospects.Neural regeneration research · 2016Review
- Nuclear Factor-Erythroid-2-Related Factor 2 in Aging and Lung Fibrosis.The American journal of pathology · 2016Review
- Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a.Free radical biology & medicine · 2015Article
- Oxidative stress response and Nrf2 signaling in aging.Free radical biology & medicine · 2015Review
- How fisetin reduces the impact of age and disease on CNS function.Frontiers in bioscience (Scholar edition) · 2015Review
- Poly(ADP-ribose) polymerase-1 modulates Nrf2-dependent transcription.Free radical biology & medicine · 2014Article
- Stress proteins in aging and life span.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2013Review
- Glutathione (GSH) and the GSH synthesis gene Gclm modulate plasma redox and vascular responses to acute diesel exhaust inhalation in mice.Inhalation toxicology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
Abstract
NFE2-related factor 2 (Nrf2) transcriptionally governs the cellular response to harmful electrophiles, xenobiotics, and reactive oxygen species. Its nuclear levels decline with age (Suh et al., 2004a), which in part explains the age-related loss of phase II detoxification. However, little work has yet characterized how age affects Nrf2 DNA binding or the role that alterations to the Nrf2 transcriptional apparatus plays in modulating Nrf2-mediated gene expression. In this study, we used immunoprecipitation assays to show that Nrf2 bound to the active antioxidant response element (ARE) of the catalytic subunit of glutamate cysteine ligase (GCLC) is significantly lower in hepatic chromatin from aged vs. young rats. Moreover, the activity at this ARE locus is diminished during aging because of the presence of Bach1 and the absence of CREB-binding protein (CBP), a transcriptional repressor and co-activator, respectively. Further analysis reveals that Nrf2 occupies an alternate ARE site located -2.2 kb downstream from the normally active ARE binding site in livers of old rats, indicating an age-specific adaptation to maintain gene expression. Our results, thus, show that the conversion of Nrf2 binding from an active ARE to an alternative ARE element is not adequate to maintain basal expression of hepatic Gclc in old rats, which provides a potential mechanism for the age-related loss of glutathione synthetic and other phase II enzymes.
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Registered trials
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