RRC ID 18523
著者 Hamada N, Tanaka A, Fujita Y, Itoh T, Ono Y, Kitagawa Y, Tomimori N, Kiso Y, Akao Y, Nozawa Y, Ito M.
タイトル Involvement of heme oxygenase-1 induction via Nrf2/ARE activation in protection against H2O2-induced PC12 cell death by a metabolite of sesamin contained in sesame seeds.
ジャーナル Bioorg Med Chem
Abstract Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their metabolites on Nrf2/ARE activation in rat pheochromocytoma PC12 cells. Luciferase reporter assays showed that primary metabolites of sesamin and episesamin, SC-1 and EC-1 were the most potent ARE activators among all tested compounds. SC-1 {(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane} enhanced nuclear translocation of Nrf2 and up-regulated expression of phase II antioxidant enzymes including heme oxygenase-1 (HO-1). Treatment with SC-1 resulted in increased phosphorylation of p38 MAP kinase and transient increase in intracellular ROS levels. N-acetylcysteine (NAC) treatment abolished p38 phosphorylation as well as HO-1 induction caused by SC-1, indicating that ROS are upstream signals of p38 in Nrf2/ARE activation by SC-1. Furthermore, preconditioning with SC-1 attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Finally, treatment with a HO-1 inhibitor, Zn-protoporphyrin (ZnPP), and overexpression of a dominant-negative mutant of Nrf2 diminished SC-1-mediated neuroprotection. Our results demonstrate that SC-1 is capable of protecting against oxidative stress-induced neuronal cell death in part through induction of HO-1 via Nrf2/ARE activation, suggesting its potential to reduce oxidative stress and ameliorate oxidative stress-related neurodegenerative diseases.
巻・号 19(6)
ページ 1959-65
公開日 2011-3-15
DOI 10.1016/j.bmc.2011.01.059
PII S0968-0896(11)00088-5
PMID 21345685
MeSH Animals Apoptosis* Dioxoles / chemistry Dioxoles / metabolism* Dioxoles / pharmacology Heme Oxygenase-1 / chemistry Heme Oxygenase-1 / metabolism* Hydrogen Peroxide / metabolism* Lignans / chemistry Lignans / metabolism* Lignans / pharmacology NF-E2-Related Factor 2 / metabolism* PC12 Cells Rats Seedlings / chemistry Sesamum / chemistry*
IF 3.073
引用数 29
WOS 分野 CHEMISTRY, MEDICINAL CHEMISTRY, ORGANIC BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 PC-12(RCB0009)