Involvement of lipid rafts on Nrf2 activation induced by quercetin

抄録

Quercetin is one of the flavonoids and has a wide variety of cytoprotective effects. We previously reported that quercetin exerted various cytoprotective effects via nuclear factor E2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway. However, the mechanisms how quercetin can induce HO-1 to exhibit cytoprotective effects are poorly understood. We focused on cell membrane, which is the front line to interact with extracellular environment and plays an important role in cellular signaling. Recent studies showed that Nrf2 interacted with caveolin-1 (Cav-1), a component of caveolae, to regulate cellular anti-oxidant capacity. In this study, we investigated the involvement of Cav-1 in quercetin-induced HO-1 expression. We showed that quercetin changed the formation of lipid rafts, and the expression level of Cav-1 was decreased in cell membrane and increased in cytosol and nucleus after exposure to quercetin. The expression level of Nrf2 localized in cell membrane was also decreased, and Nrf2 was translocated to cytosol and nucleus. The extent of HO-1 induction by quercetin was as much as that by methyl-beta-cyclodextrin, a cholesterol-depleting agent. These findings suggested that HO-1-dependent cytoprotective effects by quercetin could be mediated through the disruption of lipid rafts, leading Cav-1 and Nrf2 to translocate from cell membrane and to nucleus, followed by HO-1 induction.