Quercetin Induces the Expression of Peroxiredoxins 3 and 5 via the Nrf2/NRF1 Transcription Pathway

We have previously shown that oxidative stress can induce PRDX1 and PRDX5 through activation of the Ets1 transcription factor.23

Naoya Miyamoto; Hiroto Izumi; Rie Miyamoto; Hiroyuki Kondo; Akihiko Tawara; Yasuyuki Sasaguri; Kimitoshi Kohno

2010

Scholarcy highlights

  • Purpose.: The flavonoids have potent antioxidant and free-radical scavenging properties and are beneficial in the prevention and treatment of ocular diseases including glaucoma
  • Methods.: To demonstrate whether quercetin can transcriptionally induce the expression of the PRDX family, trabecular meshwork cells were treated with quercetin, and PRDX expression and transcription factors were both investigated by Western blot analysis, reporter assays, and small interfering RNA strategies
  • Reporter assays showed that NRF1 transactivated the promoter activity of both PRDX3 and PRDX5 and that the downregulation of NRF1 with siRNA repressed the promoter activity of both PRDX3 and PRDX5
  • Conclusions.: Quercetin upregulates the antioxidant peroxiredoxins through the activation of the nuclear factor-like 2/NRF1 transcription pathway and protects against oxidative stress-induced ocular disease
  • Both PRDX3 and PRDX5 were induced by 1 μM quercetin in a time-dependent manner. We found that both PRDX3 and PRDX5 were induced by quercetin treatment in a dose-dependent manner
  • PRDX1 expression could not detected in immortalized trabecular meshwork cells,24 HTMCs express PRDX1.31 We again observed that the expression of both PRDX3 and PRDX5 was induced by the treatment of HTMCs with quercetin
  • Flavonoids such as quercetin can protect cells from oxidative stress.4 Quercetin—present in fruit, vegetables, and many other dietary sources—is one of the most widely distributed flavonoids.5 It has been shown that certain flavonoids can induce antioxidant responsive element-dependent gene expression through the activation of nuclear factor-like 2.6 Oxidative stress plays an important role in the pathogenesis of multiple ocular diseases, including glaucoma.7

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