Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells.
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.
Chen
Chu-Yue
CY
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, Republic of Korea.
Jang
Jung-Hee
JH
Li
Mei-Hua
MH
Surh
Young-Joon
YJ
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*
D017931:DNA Primers; D008565:Membrane Proteins; C499194:Pex14 protein, rat; D012097:Repressor Proteins; D013267:Stilbenes; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D005721:Glutamate-Cysteine Ligase; D000077185:Resveratrol