Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress
Kubo E, Chhunchha B, Singh P, Sasaki H, Singh DP
Scientific reports · 188 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Research to Prevent Blindness
- Government
- National Institutes of Health
- Government
- National Eye Institute
- Government
- NEI NIH HHS
- Grants
- National Eye Institute (EY024589); National Eye Institute (R01 EY024589); National Institutes of Health (EY024589)
Based on 4 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2017-10-20 · Sci Rep · vol. 7 · issue 1 · p. 14130
- Publisher
- Nature Portfolio
- Cited
- 231 citations · more than 98% of similar papers · 6.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 93 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Selenium in Biological Systems · Redox biology and oxidative stress
- Keywords
- Sulforaphane, Oxidative stress, Gene knockdown, Cytoprotection, Activator (genetics), Chemistry, Transcription factor, DNA damage, Catalase, Cell biology, Antioxidant, Molecular biology, Electrophoretic mobility shift assay, Biology, Apoptosis, Biochemistry, Gene, DNA
- MeSH
- cell nucleus, animals, humans, rats, rats, sprague-dawley, isothiocyanates, sulfoxides, antioxidants, transcription, genetic, gene expression regulation, up-regulation, response elements, active transport, cell nucleus, oxidative stress, aging, dose-response relationship, drug, time factors, adolescent, adult, aged, middle aged, nf-e2-related factor 2, peroxiredoxin vi, promoter regions, genetic, young adult
5 authors
From JP, US
- Eri Kubo · correspondingKanazawa University; Kanazawa Medical University; Kanazawa Medical Center
- Bhavana ChhunchhaUniversity of Nebraska Medical Center
- Prerna SinghUniversity of Nebraska Medical Center
- Hiroshi SasakiKanazawa Medical University
- Dhirendra Pratap Singh · correspondingNebraska Medical Center; University of Nebraska Medical Center
Abstract
Upon oxidative stress and aging, Nrf2 (NFE2-related factor2) triggers antioxidant defense genes to defends against homeostatic failure. Using human(h) or rat(r) lens epithelial cells (LECs) and aging human lenses, we showed that a progressive increase in oxidative load during aging was linked to a decline in Prdx6 expression. DNA binding experiments using gel-shift and ChIP assays demonstrated a progressive reduction in Nrf2/ARE binding (-357/-349) of Prdx6 promoter. The promoter (-918) with ARE showed a marked reduction in young vs aged hLECs, which was directly correlated to decreased Nrf2/ARE binding. A Nrf2 activator, Sulforaphane (SFN), augmented Prdx6, catalase and GSTπ expression in dose-dependent fashion, and halted Nrf2 dysregulation of these antioxidants. SFN reinforced Nrf2/DNA binding and increased promoter activities by enhancing expression and facilitating Nrf2 translocalization in nucleus. Conversely, promoter mutated at ARE site did not respond to SFN, validating the SFN-mediated restoration of Nrf2/ARE signaling. Furthermore, SFN rescued cells from UVB-induced toxicity in dose-dependent fashion, which was consistent with SFN's dose-dependent activation of Nrf2/ARE interaction. Importantly, knockdown of Prdx6 revealed that Prdx6 expression was prerequisite for SFN-mediated cytoprotection. Collectively, our results suggest that loss of Prdx6 caused by dysregulation of ARE/Nrf2 can be attenuated through a SFN, to combat diseases associated with aging.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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