The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells
Abstract
Resveratrol (3,4',5-trihydroxy stilbene), a phytoalexin found in the skin and seeds of grapes, has been reported to possess anti-inflammatory, anticarcinogenic, and antioxidant activities. In this work, we assessed the ability of resveratrol to upregulate heme oxygenase-1 (HO-1) gene expression via activation of NF-E2-related factor 2 (Nrf2) in cultured PC12 cells. Nrf2 is a transcription factor involved in the cellular protection against oxidative stress through antioxidant response element (ARE)-directed induction of several phase 2 detoxifying and antioxidant enzymes, such as HO-1. Here, we report that resveratrol induces HO-1 expression via the ARE-mediated transcriptional activation of Nrf2. Moreover, PC12 cells treated with resveratrol exhibited transient activation of Akt/protein kinase B and extracellular signal-regulated protein kinase 1/2 (ERK1/2). LY294002 and U0126, pharmacological inhibitors of phosphatidylinositol 3-kinase and MEK1/2 which are upstream of Akt and ERK1/2, respectively, attenuated resveratrol-induced HO-1 expression and exhibited antioxidant effects. Taken together, the above findings suggest that resveratrol augments cellular antioxidant defense capacity through induction of HO-1 via Nrf2-ARE signaling, thereby protecting PC12 cells from oxidative stress.
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“Nrf2 is a pro‐longevity signaling pathway (Harman, 2006) and also a key mediator of the beneficial effects of calorie restriction.”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Chen et al., 2005
In the citing paper
“in C. elegans, drugs believed to be ‘calorie restriction mimetics’ (resveratrol, metformin, and rapamycin) activate the Nrf2 signaling pathway as part of their mechanism of lifespan extension”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Chen et al., 2005
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Nrf2, a Cap'n'Collar Transcription Factor, Regulates Induction of the Heme Oxygenase-1 Gene
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Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element
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Dietary polyphenols and their biological significance
Han, X., Shen, T., & Lou, H. (2007) · International Journal of Molecular Sciences · doi:10.3390/i8090950 · Cited by 1,081
The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation
Bryan, H. K., Olayanju, A., Goldring, C. E., & Park, B. K. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.11.016 · Cited by 1,047
Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation
Hybertson, B. M., Gao, B., Bose, S. K., & McCord, J. M. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.006 · Cited by 1,046
Regulation of inflammation and redox signaling by dietary polyphenols
Rahman, I., Biswas, S. K., & Kirkham, P. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.004 · Cited by 1,003
Surh, Y., Kundu, J. K., & Na, H. (2008) · Planta Medica · doi:10.1055/s-0028-1088302 · Cited by 758
Self-citation
Metadata
- Authors
- Chen, C.-Y., Jang, J.-H., Li, M.-H., & Surh, Y.-J.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Surh, Young-Joon
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 331
- Issue
- 4
- Pages
- 993-1000
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2073679813
- Cited by
- 428
- References
- 48
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 19 · 2020: 23 · 2019: 22 · 2018: 9 · 2017: 25 · 2016: 16 · 2015: 29 · 2014: 27 · 2013: 25 · 2012: 28
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Fonds National de la Recherche Luxembourg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- resveratrol, heme oxygenase-1, Nrf2, antioxidant response element, PC12 cells, oxidative stress, Akt signaling, ERK signaling, phosphatidylinositol 3-kinase, MEK1/2, antioxidant defense, transcriptional activation
- MeSH terms
- Resveratrol, Animals, Base Sequence, Enzyme Induction, Glutamate-Cysteine Ligase, Heme Oxygenase (Decyclizing), Hydrogen Peroxide, Membrane Proteins, Phosphorylation, Repressor Proteins, Stilbenes, Gene Expression Regulation, Enzymologic, PC12 Cells, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Rats
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