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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.
- Source :
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Bioorganic & medicinal chemistry [Bioorg Med Chem] 2011 Mar 15; Vol. 19 (6), pp. 1959-65. Date of Electronic Publication: 2011 Feb 02. - Publication Year :
- 2011
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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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Dioxoles chemistry
Dioxoles pharmacology
Heme Oxygenase-1 chemistry
Lignans chemistry
Lignans pharmacology
PC12 Cells
Rats
Seedlings chemistry
Apoptosis
Dioxoles metabolism
Heme Oxygenase-1 metabolism
Hydrogen Peroxide metabolism
Lignans metabolism
NF-E2-Related Factor 2 metabolism
Sesamum chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 19
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21345685
- Full Text :
- https://doi.org/10.1016/j.bmc.2011.01.059