Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes.
10.4062/biomolther.2014.121
- Author:
Yeon Hui JEONG
1
;
Jin Sun PARK
;
Dong Hyun KIM
;
Hee Sun KIM
Author Information
1. Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 158-710, Republic of Korea. hskimp@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Arctigenin;
Astrocyte;
Hemeoxygenase-1;
PI3K/AKT;
Nrf2/ARE axis
- MeSH:
Animals;
Antioxidant Response Elements;
Astrocytes*;
Axis, Cervical Vertebra;
Brain;
DNA;
Gene Expression*;
Hydrogen;
Phosphatidylinositol 3-Kinase;
Phosphorylation;
Rats*;
Reactive Oxygen Species;
RNA, Messenger
- From:Biomolecules & Therapeutics
2014;22(6):497-502
- CountryRepublic of Korea
- Language:English
-
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.
