Cited by 428Genomics, phytochemicals, and oxidative stressHeme Oxygenase-1 and Carbon MonoxideSirtuins and Resveratrol in Medicine

Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells

Chen, Chu-Yue, Jang, Jung-Hee, Li, Mei-Hua, Surh, Young-Joon·2005·Biochemical and Biophysical Research Communications

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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Crossref · 10.1016/j.bbrc.2005.03.237

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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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