Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
BMC Medicine (Impact Factor: 7.28). 09/2010; 8:54. DOI: 10.1186/1741-7015-8-54
Source: PubMed

ABSTRACT Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819
In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays.
Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups.
The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes.


Available from: Asim K Duttaroy, May 02, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mushrooms represent a remarkable and yet largely unexplored source of new, biologically active natural products. In this work, we report on the xanthine oxidase (XO) inhibitory activity of 47 wild-growing mushrooms native to Hungary. Aqueous and organic (n-hexane, chloroform, and 50% methanol) extracts of selected mushrooms from different families were screened for their XO inhibitory activities. Among the 188 extracts investigated, the chloroform and 50% methanol fractions proved to be the most effective. Some species exhibited high inhibitory activity, e.g., Hypholoma fasciculare (IC50 = 67.76 ± 11.05 µg/mL), Suillus grevillei (IC50 = 13.28 ± 1.58 µg/mL), and Tricholoma populinum (IC50 = 85.08 ± 15.02 µg/mL); others demonstrated moderate or weak activity. Additional studies are warranted to characterize the compounds responsible for the XO inhibitory activity of mushroom extracts. Copyright © 2014 John Wiley & Sons, Ltd.
    Phytotherapy Research 08/2014; 28(8). DOI:10.1002/ptr.5115 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although early studies suggested that coffee consumption might increase risk of some cancers, more comprehensive epidemiological and experimental data now generally indicate either neutral or beneficial effects. In this review, we summarize the current evidence for associations between breast, prostate, colorectal, and liver cancers and the consumption of coffee, and discuss the experimental evidence for potential chemopreventive mechanisms of coffee and coffee constituents. The epidemiological evidence consistently indicates that coffee protects against liver cancer, and also point toward protective effects for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42-0.59) and 0.83 (95% CI: 0.75-0.92), respectively, in the most recent meta-analyses). There seems to be no association between the overall risk of breast and prostate cancer and coffee intake. However, for subgroups such as postmenopausal breast cancers, advanced prostate cancers, and breast and prostate cancer survivors, an inverse association with coffee intake is indicated. Potential mechanisms for chemopreventive effects of coffee phytochemicals includes inhibition of oxidative stress and oxidative damage, regulation of DNA repair, phase II enzymatic activity, apoptosis, inflammation, as well as having antiproliferative, antiangiogenetic effects and antimetastatic effects. The experimental evidence for effects of coffee and coffee constituents on each of these processes is discussed.
    Molecular Nutrition & Food Research 05/2014; 58(5). DOI:10.1002/mnfr.201300526 · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Fish oil supplementation has been shown to alter gene expression of mononuclear cells both in vitro and in vivo. However, little is known about the total transcriptome profile in healthy subjects after intake of fish oil. We therefore investigated the gene expression profile in peripheral blood mononuclear cells (PBMCs) after intake of fish oil for 7 weeks using transcriptome analyses.DesignIn a 7-week, double-blinded, randomized, controlled, parallel-group study, healthy subjects received 8 g/day fish oil (1.6 g/day eicosapentaenoic acid + docosahexaenoic acid) (n = 17) or 8 g/day high oleic sunflower oil (n = 19). Microarray analyses of RNA isolated from PBMCs were performed at baseline and after 7 weeks of intervention.ResultsCell cycle, DNA packaging and chromosome organization are biological processes found to be upregulated after intake of fish oil compared to high oleic sunflower oil using a moderated t-test. In addition, gene set enrichment analysis identified several enriched gene sets after intake of fish oil. The genes contributing to the significantly different gene sets in the subjects given fish oil compared to the control group are involved in cell cycle, endoplasmic reticulum (ER) stress and apoptosis. Gene transcripts with common motifs for 35 known transcription factors including E2F, TP53 and ATF4 were upregulated after intake of fish oil.Conclusion We have shown that intake of fish oil for 7 weeks modulates gene expression in PBMCs of healthy subjects. The increased expression of genes related to cell cycle, ER stress and apoptosis suggests that intake of fish oil may modulate basic cellular processes involved in normal cellular function.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 03/2014; 276(5). DOI:10.1111/joim.12217 · 5.79 Impact Factor