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

Biochem Biophys Res Commun. 2005 Jun 17;331(4):993-1000. doi: 10.1016/j.bbrc.2005.03.237.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Enzyme Induction
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Glutamate-Cysteine Ligase / biosynthesis
  • Heme Oxygenase (Decyclizing) / genetics*
  • Hydrogen Peroxide / pharmacology
  • Membrane Proteins / metabolism*
  • PC12 Cells
  • Phosphorylation
  • Rats
  • Repressor Proteins / metabolism*
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stilbenes / pharmacology*

Substances

  • DNA Primers
  • Membrane Proteins
  • Pex14 protein, rat
  • Repressor Proteins
  • Stilbenes
  • Hydrogen Peroxide
  • Heme Oxygenase (Decyclizing)
  • Glutamate-Cysteine Ligase
  • Resveratrol