Tetrachlorobenzoquinone activates Nrf2 signaling by Keap1 cross-linking and ubiquitin translocation but not Keap1-Cullin3 complex dissociation

Chemical Research in Toxicology
Chuanyang SuYang Song

Abstract

Tetrachlorobenzoquinone (TCBQ), a metabolite of industrial herbicide pentachlorophenol, showed hepatotoxicity and genotoxicity through reactive oxygen species (ROS) mechanism in vivo and in vitro models. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of oxidative or electrophilic stress, which controls the expression of detoxifying enzymes and antioxidant proteins. Using the human hepatoma HepG2 cell line as an in vitro model, we demonstrated a significant induction of Nrf2 but not its negative regulator Kelch-like ECH-associated protein 1 (Keap1), following exposure to TCBQ. Also, our results clearly demonstrated the translocation of cytosolic Nrf2 into the nucleus. After translocation, Nrf2 subsequently binds to the antioxidant response element (ARE), up-regulated heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase subunit 1 (NQO1), which may be considered as an antioxidative response to TCBQ-intoxication. The luciferase reporter assay confirmed the formation of the Nrf2-ARE complex. Furthermore, mechanism studies proposed that TCBQ promoted the formation of the Keap1 cross-linking dimer, a ubiquitination switch from Nrf2 to Keap1 but not the dissociation of the Keap1-Cullin3 (Cul3) complex.

References

Jan 1, 1996·Archives of Toxicology·M DahlhausK E Appel
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Ramos-GomezT W Kensler
Nov 24, 2001·Mutation Research·Martin PurschkeIrene Witte
Aug 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Albena T Dinkova-KostovaPaul Talalay
Mar 26, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ken ItohMasayuki Yamamoto
Feb 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nobunao WakabayashiPaul Talalay
Nov 5, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jiang LiJeffrey Johnson
Dec 2, 2004·Molecular and Cellular Biology·Donna D ZhangMark Hannink
Jun 30, 2005·The Journal of Biological Chemistry·Fei HongDaniel C Liebler
Jul 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aimee L EgglerAndrew D Mesecar
Aug 5, 2006·Advances in Enzyme Regulation·Makoto Kobayashi, Masayuki Yamamoto
Nov 28, 2006·The Journal of Biological Chemistry·Ling GaoMichael L Freeman
Feb 7, 2008·Chemical Research in Toxicology·Girish RachakondaMichael L Freeman
Aug 30, 2008·Chemical Research in Toxicology·Ryan HollandJames C Fishbein
Jan 14, 2009·Cancer Prevention Research·Tin Oo KhorAh-Ng Kong
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yang SongGarry R Buettner
Jun 30, 2009·Toxicology and Applied Pharmacology·Konjeti R SekharMichael L Freeman
Aug 12, 2009·Free Radical Biology & Medicine·James W KasparAnil K Jaiswal
Jan 12, 2010·The Journal of Biological Chemistry·Simon FourquetMichel B Toledano
Jun 10, 2010·Cancer Research·Tao JiangDonna D Zhang
Jan 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dongmei RenDonna D Zhang
Mar 3, 2011·Archives of Toxicology·Liam Baird, Albena T Dinkova-Kostova
Dec 12, 2012·Biochemical Pharmacology·Holly K BryanB Kevin Park
Feb 26, 2013·Free Radical Biology & Medicine·Suryakant K NitureAnil K Jaiswal
May 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Itamar YadidShelley D Copley
May 31, 2013·Chemical Research in Toxicology·Yumi Abiko, Yoshito Kumagai
Dec 7, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Hui DongYang Song
Jul 16, 2014·European Journal of Medicinal Chemistry·Veda PrachayasittikulVirapong Prachayasittikul

❮ Previous
Next ❯

Citations

Sep 20, 2019·Chemistry : a European Journal·Ute WildHans-Jörg Himmel
Feb 6, 2021·Cells·Sawsan ElgoharyHend M El Tayebi
Jun 15, 2020·International Journal of Biological Macromolecules·Oladipupo A AregbesolaAdemola O Olaniran
Sep 18, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Chunlei YuYingcai Niu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.