Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress

Eri Kubo, Bhavana Chhunchha, Prerna Singh, Hiroshi Sasaki, Dhirendra P. Singh

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article number14130
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Oxidative Stress
Antioxidants
Lenses
Cytoprotection
Cell Aging
DNA
sulforafan
Catalase
Gels
Epithelial Cells
Genes

ASJC Scopus subject areas

  • General

Cite this

Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress. / Kubo, Eri; Chhunchha, Bhavana; Singh, Prerna; Sasaki, Hiroshi; Singh, Dhirendra P.

In: Scientific reports, Vol. 7, No. 1, 14130, 01.12.2017.

Research output: Contribution to journalArticle

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