Role of Catechin Quinones in the Induction of EpRE-Mediated Gene Expression

M. Muzolf-Panek, A. Gliszczynska-Swiglo, L.H.J. de Haan, J.M.M.J.G. Aarts, H. Szymusiak, J.J.M. Vervoort, B. Tyrakowska, I.M.C.M. Rietjens

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30 Citations (Scopus)

Abstract

In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a luciferase reporter gene under the expression regulation of an EpRE from the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene. The results obtained show that several, but not all, catechins tested are able to induce EpRE-mediated gene transcription, with epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), both containing a pyrogallol and a galloyl moiety, being the most powerful inducers. Moreover, it was demonstrated that the EpRE-mediated response to catechins was increased in cells with reduced cellular glutathione (GSH) levels and decreased in cells with increased levels of GSH, corroborating a role for catechin quinones. The intrinsic capacity of catechins to form quinone type metabolites upon their oxidation was demonstrated using incubations of epigallocatechin (EGC) and EGCG with tyrosinase and the GSH-trapping method. Glutathione conjugates formed in these incubations were identified as 2¿-glutathionyl-EGC, 2¿,6¿-diglutathionyl-EGC, 2¿-glutathionyl-EGCG, and 2¿,6¿-diglutathionyl-EGCG, supporting the formation of quinone type metabolites involving especially the pyrogallol moiety of these catechins. Formation of the EGCG-quinone-glutathionyl adducts was also observed in the EpRE-LUX cellular system. This further supports the importance of the pyrogallol moiety for the quinone chemistry of the catechins. Finally, the presence of the pyrogallol moiety in the catechins also results in a relatively lower half-wave oxidation potential (E1/2) and calculated heat of formation (DHF) for conversion of the catechins to their corresponding quinones, pointing at an increased ability to become oxidized. Altogether, our studies reveal that catechins, especially those containing a pyrogallol moiety, induce EpRE-mediated detoxifying gene expression and that this induction is likely to be the result of their quinone chemistry.
LanguageEnglish
Pages2352-2360
JournalChemical Research in Toxicology
Volume21
Issue number12
DOIs
Publication statusPublished - 2008

Fingerprint

Quinones
Catechin
Gene expression
Pyrogallol
Gene Expression
Genes
Metabolites
Glutathione
Oxidation
Monophenol Monooxygenase
Gene Expression Regulation
Response Elements
Tea
Transcription
Luciferases
Reporter Genes
Hepatocellular Carcinoma
Hot Temperature
epigallocatechin gallate
benzoquinone

Keywords

  • tea polyphenol (-)-epigallocatechin-3-gallate
  • activated protein-kinases
  • green tea
  • anticancer properties
  • medicinal benefits
  • phenolic-acids
  • in-vitro
  • keap1
  • nrf2
  • quercetin

Cite this

Muzolf-Panek, M. ; Gliszczynska-Swiglo, A. ; de Haan, L.H.J. ; Aarts, J.M.M.J.G. ; Szymusiak, H. ; Vervoort, J.J.M. ; Tyrakowska, B. ; Rietjens, I.M.C.M. / Role of Catechin Quinones in the Induction of EpRE-Mediated Gene Expression. In: Chemical Research in Toxicology. 2008 ; Vol. 21, No. 12. pp. 2352-2360.
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abstract = "In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a luciferase reporter gene under the expression regulation of an EpRE from the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene. The results obtained show that several, but not all, catechins tested are able to induce EpRE-mediated gene transcription, with epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), both containing a pyrogallol and a galloyl moiety, being the most powerful inducers. Moreover, it was demonstrated that the EpRE-mediated response to catechins was increased in cells with reduced cellular glutathione (GSH) levels and decreased in cells with increased levels of GSH, corroborating a role for catechin quinones. The intrinsic capacity of catechins to form quinone type metabolites upon their oxidation was demonstrated using incubations of epigallocatechin (EGC) and EGCG with tyrosinase and the GSH-trapping method. Glutathione conjugates formed in these incubations were identified as 2¿-glutathionyl-EGC, 2¿,6¿-diglutathionyl-EGC, 2¿-glutathionyl-EGCG, and 2¿,6¿-diglutathionyl-EGCG, supporting the formation of quinone type metabolites involving especially the pyrogallol moiety of these catechins. Formation of the EGCG-quinone-glutathionyl adducts was also observed in the EpRE-LUX cellular system. This further supports the importance of the pyrogallol moiety for the quinone chemistry of the catechins. Finally, the presence of the pyrogallol moiety in the catechins also results in a relatively lower half-wave oxidation potential (E1/2) and calculated heat of formation (DHF) for conversion of the catechins to their corresponding quinones, pointing at an increased ability to become oxidized. Altogether, our studies reveal that catechins, especially those containing a pyrogallol moiety, induce EpRE-mediated detoxifying gene expression and that this induction is likely to be the result of their quinone chemistry.",
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author = "M. Muzolf-Panek and A. Gliszczynska-Swiglo and {de Haan}, L.H.J. and J.M.M.J.G. Aarts and H. Szymusiak and J.J.M. Vervoort and B. Tyrakowska and I.M.C.M. Rietjens",
year = "2008",
doi = "10.1021/tx8001498",
language = "English",
volume = "21",
pages = "2352--2360",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
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Role of Catechin Quinones in the Induction of EpRE-Mediated Gene Expression. / Muzolf-Panek, M.; Gliszczynska-Swiglo, A.; de Haan, L.H.J.; Aarts, J.M.M.J.G.; Szymusiak, H.; Vervoort, J.J.M.; Tyrakowska, B.; Rietjens, I.M.C.M.

In: Chemical Research in Toxicology, Vol. 21, No. 12, 2008, p. 2352-2360.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Role of Catechin Quinones in the Induction of EpRE-Mediated Gene Expression

AU - Muzolf-Panek, M.

AU - Gliszczynska-Swiglo, A.

AU - de Haan, L.H.J.

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

AU - Szymusiak, H.

AU - Vervoort, J.J.M.

AU - Tyrakowska, B.

AU - Rietjens, I.M.C.M.

PY - 2008

Y1 - 2008

N2 - In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a luciferase reporter gene under the expression regulation of an EpRE from the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene. The results obtained show that several, but not all, catechins tested are able to induce EpRE-mediated gene transcription, with epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), both containing a pyrogallol and a galloyl moiety, being the most powerful inducers. Moreover, it was demonstrated that the EpRE-mediated response to catechins was increased in cells with reduced cellular glutathione (GSH) levels and decreased in cells with increased levels of GSH, corroborating a role for catechin quinones. The intrinsic capacity of catechins to form quinone type metabolites upon their oxidation was demonstrated using incubations of epigallocatechin (EGC) and EGCG with tyrosinase and the GSH-trapping method. Glutathione conjugates formed in these incubations were identified as 2¿-glutathionyl-EGC, 2¿,6¿-diglutathionyl-EGC, 2¿-glutathionyl-EGCG, and 2¿,6¿-diglutathionyl-EGCG, supporting the formation of quinone type metabolites involving especially the pyrogallol moiety of these catechins. Formation of the EGCG-quinone-glutathionyl adducts was also observed in the EpRE-LUX cellular system. This further supports the importance of the pyrogallol moiety for the quinone chemistry of the catechins. Finally, the presence of the pyrogallol moiety in the catechins also results in a relatively lower half-wave oxidation potential (E1/2) and calculated heat of formation (DHF) for conversion of the catechins to their corresponding quinones, pointing at an increased ability to become oxidized. Altogether, our studies reveal that catechins, especially those containing a pyrogallol moiety, induce EpRE-mediated detoxifying gene expression and that this induction is likely to be the result of their quinone chemistry.

AB - In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a luciferase reporter gene under the expression regulation of an EpRE from the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene. The results obtained show that several, but not all, catechins tested are able to induce EpRE-mediated gene transcription, with epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), both containing a pyrogallol and a galloyl moiety, being the most powerful inducers. Moreover, it was demonstrated that the EpRE-mediated response to catechins was increased in cells with reduced cellular glutathione (GSH) levels and decreased in cells with increased levels of GSH, corroborating a role for catechin quinones. The intrinsic capacity of catechins to form quinone type metabolites upon their oxidation was demonstrated using incubations of epigallocatechin (EGC) and EGCG with tyrosinase and the GSH-trapping method. Glutathione conjugates formed in these incubations were identified as 2¿-glutathionyl-EGC, 2¿,6¿-diglutathionyl-EGC, 2¿-glutathionyl-EGCG, and 2¿,6¿-diglutathionyl-EGCG, supporting the formation of quinone type metabolites involving especially the pyrogallol moiety of these catechins. Formation of the EGCG-quinone-glutathionyl adducts was also observed in the EpRE-LUX cellular system. This further supports the importance of the pyrogallol moiety for the quinone chemistry of the catechins. Finally, the presence of the pyrogallol moiety in the catechins also results in a relatively lower half-wave oxidation potential (E1/2) and calculated heat of formation (DHF) for conversion of the catechins to their corresponding quinones, pointing at an increased ability to become oxidized. Altogether, our studies reveal that catechins, especially those containing a pyrogallol moiety, induce EpRE-mediated detoxifying gene expression and that this induction is likely to be the result of their quinone chemistry.

KW - tea polyphenol (-)-epigallocatechin-3-gallate

KW - activated protein-kinases

KW - green tea

KW - anticancer properties

KW - medicinal benefits

KW - phenolic-acids

KW - in-vitro

KW - keap1

KW - nrf2

KW - quercetin

U2 - 10.1021/tx8001498

DO - 10.1021/tx8001498

M3 - Article

VL - 21

SP - 2352

EP - 2360

JO - Chemical Research in Toxicology

T2 - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 12

ER -