title: Fisetin induces Nrf2-mediated HO-1 expression through PKC-δ and p38 in human umbilical vein endothelial cells.
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(2)O(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(2)O(2) -induced oxidative stress in HUVECs.
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Seong Il
authors.initials: SI
authors.lastname: Jeong
authors.forename: Hana
authors.initials: H
authors.lastname: Yang
authors.forename: Cheung-Seog
authors.initials: CS
authors.lastname: Park
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Jin
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D019610:Cytoprotection; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000378:metabolism*; D011524:Protoporphyrins / Q000494:pharmacology; D020218:Response Elements; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D044948:Flavonols; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016877:Oxidants; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006861:Hydrogen Peroxide; D008156:Luciferases; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051745:Protein Kinase C-delta; D048051:p38 Mitogen-Activated Protein Kinases; C017875:fisetin