Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2

BMC Complementary and Alternative Medicine

Research Article

Seiichi Matsugo¹  Koji Hashida²  Osamu Hori²  Frank Döring³  Dorothea Breckwoldt³  Christine Boesch-Saadatmandi³  Anika E Wagner³  Charlotte Schrader³  Constance Schmelzer³  Gerald Rimbach³ 

[1] College of Science and Engineering, School of Natural System, Kanazawa University, 920-1192, Kakuma, Kanazawa, Japan;Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, 920-1192, Kakuma, Kanazawa, Japan;Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Hermann-Rodewald-Str. 6, 24118, Kiel, Germany;

关键词: Ascorbic Acid;    Resveratrol;    HUH7 Cell;    PON1 Gene;    Nrf2 Signalling Pathway;   

DOI  :  10.1186/1472-6882-11-1

 received in 2010-10-01, accepted in 2011-01-03,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundBoth resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid.MethodsThe antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays.ResultsHere, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid.ConclusionsUnlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.

【 授权许可】

Unknown   
© Wagner et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.