The mechanisms of Nrf2-HO-1 activation and cytoprotective effects induced by flavonoids

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860187
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Nagoya University
• Principal Investigator: MATSUSHIMA Miyoko 名古屋大学, 医学(系)研究科(研究院), 助教 (10509665)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: フラボノイド / Nrf2 / heme oxygenase-1

Outline of Final Research Achievements

Flavonoids are known to exhibit various cytoprotective effects. In this study, we investigated the mechanisms of Nrf2 activation and cytoprotective effects induced by flavonoids. We found the chrysin, one of the flavonoids, had cytoprotective effect without HO-1 induction. We compared the effect of quercetin, which can induce HO-1, and chrysin on the inhibition of mast cell activation, and suggested that HO-1 might regulate signaling events before calcium mobilization associated with mast cell activation. We also focused on caveolin-1 (Cav-1), with which Nrf2 interacted in cell membrane to regulate cellular anti-oxidant capacity. We showed that quercetin changed the formation of lipid rafts, and the expression level of Cav-1 and Nrf2 was decreased in cell membrane and increased in cytosol and nucleus after exposure to quercetin. These results suggested that the disruption of lipid rafts would translocate Cav-1 and Nrf2 from cell membrane and to nucleus, leading to HO-1 induction.

Free Research Field

薬理学