Fisetin induces Nrf2-mediated HO-1 expression through PKC-δ and p38 in human umbilical vein endothelial cells

Seung Eun Lee, Seong Il Jeong, Hana Yang, Cheung Seog Park, Young Ho Jin, Yong Seek Park

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Fisetin is a natural flavonoid from fruits and vegetables that exhibits antioxidant, neurotrophic, anti-inflammatory, and anti-cancer effects in various disease models. Up-regulation of heme oxygenase-1 (HO-1) expression protects against oxidative stress-induced cell death, and therefore, plays a crucial role in cytoprotection in a variety of pathological models. In the present study, we investigated the effect of fisetin on the up-regulation of HO-1 in human umbilical vein endothelial cells (HUVECs). Small interfering RNA and pharmacological inhibitors of PKC-δ and p38 MAPK attenuated HO-1 induction in fisetin-stimulated HUVECs. Fisetin treatment resulted in significantly increased NF-E2-related factor 2 (Nrf2) nuclear translocation, and antioxidant response element (ARE)-luciferase activity, leading to up-regulation of HO-1 expression. In addition, fisetin pretreatment reduced hydrogen peroxide (H 2O 2)-induced cell death, and this effect was reversed by ZnPP, an inhibitor of HO-1. In summary, these findings suggest that induction of HO-1 expression via Nrf2 activation may contribute to the cytoprotection exerted by fisetin against H 2O 2-induced oxidative stress in HUVECs.

Original languageEnglish (US)
Pages (from-to)2352-2360
Number of pages9
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
StatePublished - Sep 1 2011

Keywords

  • Endothelial cells
  • Fisetin
  • HO-1
  • Nrf2
  • Oxidative stress

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