Combining an in vitro reporter gene assay with metabolomics to identify tomato phytochemicals responsible for inducing electrophile-responsive element (EpRE)-mediated gene transcription

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Abstract

The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression effects of certain dietary compounds. In this study we measured the ability of extracts of glycosidase treated tomato fruits from 97 different accessions to induce EpRE-mediated luciferase expression using EpRE-LUX reporter cells and analyzed the same extracts using LC–MSbased untargeted metabolomics profiling. We were able to pinpoint those tomato compounds that were most correlated with EpRE-mediated luciferase induction, by combining reporter gene assay data with the metabolic profiles of the same extracts. Flavonoids were the compounds showing the strongest positive correlation with EpRE-LUX activity. These results were validated using a transgenic tomato line accumulating high levels of flavonoids. Results obtained corroborated that flavonoids are an important determinant of the ability of tomato fruit extracts to induce EpRE-mediated beneficial health effects. Overall, these results indicate that combining untargeted metabolomics with reporter gene assays provides a powerful tool for nutritionists, plant breeders and food chemists towards identification of potential health-beneficial constituents of tomato fruits, as well as of other crops and products derived thereof.
Original languageEnglish
Pages (from-to)302-311
JournalMetabolomics
Volume11
Issue number2
DOIs
Publication statusPublished - 2015

Fingerprint

Metabolomics
Phytochemicals
Transcription
Lycopersicon esculentum
Fruits
Reporter Genes
Flavonoids
Assays
Genes
Luciferases
Fruit
Health
Glycoside Hydrolases
Gene expression
Crops
Edible Plants
Metabolome
Nutritionists
Neoplasm Genes
In Vitro Techniques

Keywords

  • solanum-lycopersicon
  • mass-spectrometry
  • fruit
  • expression
  • health
  • metabolism
  • flavonoids
  • lycopene
  • deglycosylation
  • polyphenols

Cite this

@article{773e73fd8621476796de20aa4b019499,
title = "Combining an in vitro reporter gene assay with metabolomics to identify tomato phytochemicals responsible for inducing electrophile-responsive element (EpRE)-mediated gene transcription",
abstract = "The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression effects of certain dietary compounds. In this study we measured the ability of extracts of glycosidase treated tomato fruits from 97 different accessions to induce EpRE-mediated luciferase expression using EpRE-LUX reporter cells and analyzed the same extracts using LC–MSbased untargeted metabolomics profiling. We were able to pinpoint those tomato compounds that were most correlated with EpRE-mediated luciferase induction, by combining reporter gene assay data with the metabolic profiles of the same extracts. Flavonoids were the compounds showing the strongest positive correlation with EpRE-LUX activity. These results were validated using a transgenic tomato line accumulating high levels of flavonoids. Results obtained corroborated that flavonoids are an important determinant of the ability of tomato fruit extracts to induce EpRE-mediated beneficial health effects. Overall, these results indicate that combining untargeted metabolomics with reporter gene assays provides a powerful tool for nutritionists, plant breeders and food chemists towards identification of potential health-beneficial constituents of tomato fruits, as well as of other crops and products derived thereof.",
keywords = "solanum-lycopersicon, mass-spectrometry, fruit, expression, health, metabolism, flavonoids, lycopene, deglycosylation, polyphenols",
author = "{van Eekelen}, H.D.L.M. and L. Gijsbers and C.A. Maliepaard and R.A.M. Vreeburg and H.J. Finkers and Y.M. Tikunov and {Gomez Roldan}, M.V. and {de Haan}, L.H.J. and {de Vos}, R.C.H. and J.M.M.J.G. Aarts and I. Rietjens and A.G. Bovy",
year = "2015",
doi = "10.1007/s11306-014-0694-2",
language = "English",
volume = "11",
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T1 - Combining an in vitro reporter gene assay with metabolomics to identify tomato phytochemicals responsible for inducing electrophile-responsive element (EpRE)-mediated gene transcription

AU - van Eekelen, H.D.L.M.

AU - Gijsbers, L.

AU - Maliepaard, C.A.

AU - Vreeburg, R.A.M.

AU - Finkers, H.J.

AU - Tikunov, Y.M.

AU - Gomez Roldan, M.V.

AU - de Haan, L.H.J.

AU - de Vos, R.C.H.

AU - Aarts, J.M.M.J.G.

AU - Rietjens, I.

AU - Bovy, A.G.

PY - 2015

Y1 - 2015

N2 - The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression effects of certain dietary compounds. In this study we measured the ability of extracts of glycosidase treated tomato fruits from 97 different accessions to induce EpRE-mediated luciferase expression using EpRE-LUX reporter cells and analyzed the same extracts using LC–MSbased untargeted metabolomics profiling. We were able to pinpoint those tomato compounds that were most correlated with EpRE-mediated luciferase induction, by combining reporter gene assay data with the metabolic profiles of the same extracts. Flavonoids were the compounds showing the strongest positive correlation with EpRE-LUX activity. These results were validated using a transgenic tomato line accumulating high levels of flavonoids. Results obtained corroborated that flavonoids are an important determinant of the ability of tomato fruit extracts to induce EpRE-mediated beneficial health effects. Overall, these results indicate that combining untargeted metabolomics with reporter gene assays provides a powerful tool for nutritionists, plant breeders and food chemists towards identification of potential health-beneficial constituents of tomato fruits, as well as of other crops and products derived thereof.

AB - The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression effects of certain dietary compounds. In this study we measured the ability of extracts of glycosidase treated tomato fruits from 97 different accessions to induce EpRE-mediated luciferase expression using EpRE-LUX reporter cells and analyzed the same extracts using LC–MSbased untargeted metabolomics profiling. We were able to pinpoint those tomato compounds that were most correlated with EpRE-mediated luciferase induction, by combining reporter gene assay data with the metabolic profiles of the same extracts. Flavonoids were the compounds showing the strongest positive correlation with EpRE-LUX activity. These results were validated using a transgenic tomato line accumulating high levels of flavonoids. Results obtained corroborated that flavonoids are an important determinant of the ability of tomato fruit extracts to induce EpRE-mediated beneficial health effects. Overall, these results indicate that combining untargeted metabolomics with reporter gene assays provides a powerful tool for nutritionists, plant breeders and food chemists towards identification of potential health-beneficial constituents of tomato fruits, as well as of other crops and products derived thereof.

KW - solanum-lycopersicon

KW - mass-spectrometry

KW - fruit

KW - expression

KW - health

KW - metabolism

KW - flavonoids

KW - lycopene

KW - deglycosylation

KW - polyphenols

U2 - 10.1007/s11306-014-0694-2

DO - 10.1007/s11306-014-0694-2

M3 - Article

VL - 11

SP - 302

EP - 311

JO - Metabolomics

JF - Metabolomics

SN - 1573-3882

IS - 2

ER -