title: Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes.
abstract: In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.
authors.affiliation: Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 158-710.
authors.forename: Yeon-Hui
authors.initials: YH
authors.lastname: Jeong
authors.affiliation: Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 158-710.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Park
authors.affiliation: Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 158-710.
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Kim
keywords: Arctigenin; Astrocyte; Hemeoxygenase-1; Nrf2/ARE axis; PI3K/AKT