Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator

Abiko, Yoshihiro; Lin, Feng-Sheng; Lee, Hsinyu; Puga, Alvaro; Kumagai, Yoshito

doi:10.2131/jts.41.775

Cited by 9 publications

(10 citation statements)

References 25 publications

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“…The expression of this isozyme is regulated by the pregnane X receptor and the constitutive androstane receptor in the liver, but little is known about its regulation in brain [ 25 ]. CYP1A1 is an inducible isoform that can be regulated by aryl hydrocarbon receptors (AhR) [ 26 , 27 ]. Its expression has been related to some brain areas, yet its main role in neuronal cells is not well known [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP+ Toxicity in Human Neuroblastoma SH-SY5Y Cells

Fernandez-Abascal

Ripullone

Valeri

et al. 2018

IJMS

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Cytochrome P450 (CYP) isozymes vary their expression depending on the brain area, the cell type, and the presence of drugs. Some isoforms are involved in detoxification and/or toxic activation of xenobiotics in central nervous system. However, their role in brain metabolism and neurodegeneration is still a subject of debate. We have studied the inducibility of CYP isozymes in human neuroblastoma SH-SY5Y cells, treated with β-naphtoflavone (β-NF) or ethanol (EtOH) as inducers, by qRT-PCR, Western blot (WB), and metabolic activity assays. Immunohistochemistry was used to localize the isoforms in mitochondria and/or endoplasmic reticulum (ER). Tetrazolium (MTT) assay was performed to study the role of CYPs during methylphenyl pyridine (MPP+) exposure. EtOH increased mRNA and protein levels of CYP2D6 by 73% and 60% respectively. Both β-NF and EtOH increased CYP2E1 mRNA (4- and 1.4-fold, respectively) and protein levels (64% both). The 7-ethoxycoumarin O-deethylation and dextromethorphan O-demethylation was greater in treatment samples than in controls. Furthermore, both treatments increased by 22% and 18%, respectively, the cell viability in MPP+-treated cells. Finally, CYP2D6 localized at mitochondria and ER. These data indicate that CYP is inducible in SH-SY5Y cells and underline this in vitro system for studying the role of CYPs in neurodegeneration.

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Section: Introductionmentioning

confidence: 99%

β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP+ Toxicity in Human Neuroblastoma SH-SY5Y Cells

Fernandez-Abascal

Ripullone

Valeri

et al. 2018

IJMS

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“…1,2-NQ and 1,4-NQ were previously reported by Akibo et al [29,30] to activate the AhR and induce AhR-dependent gene transcription in mice. Prior to more extensive analysis of the specific interactions of these compounds with the AhR, we first confirmed that 1,2-NQ and 1,4-NQ stimulated induction of the AhR-responsive gene CYP1A1/cyp1a1 in human and mouse hepatoma cells, respectively, in a concentration-dependent manner ( Figure 2).…”

Section: 2-nq and 14-nq Induce Ahr-dependent Gene Expression In Momentioning

confidence: 65%

“…Highly reactive quinone metabolites are known to stimulate electrophilic signal transduction pathways by their ability to covalently modify and activate transcription factors such as nuclear factor erythroid 2-related factor 2 (NRF2) [1,2]. Recently, quinone metabolites of NA (1,2-NQ and 1,4-NQ) as well as 1,4-benzoquinone, tert-butyl-1,4-benzoquinone, and other electrophilic mono-and di-cyclic quinones with covalent binding capacity were observed to upregulate CYP1A1/cyp1a1 mRNA in human HepG2 and mouse hepa1c1c7 cells, while the parent compounds had little effect [29,30]. Further, some quinones, including 1,2-NQ and 1,4-NQ, simulate AhR nuclear translocation and induction of cyp1a1 in mouse hepatoma cells in an AhR-dependent manner and the induction could be blocked by an AhR antagonist.…”

Section: Introductionmentioning

confidence: 99%

The Cellular and Molecular Determinants of Naphthoquinone-Dependent Activation of the Aryl Hydrocarbon Receptor

Faber

Tagliabue

Bonati

et al. 2020

IJMS

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1,2-naphthoquinone (1,2-NQ) and 1,4-naphthoquinone (1,4-NQ) are clinically promising biologically active chemicals that have been shown to stimulate the aryl hydrocarbon receptor (AhR) signaling pathway, but whether they are direct or indirect ligands or activate the AhR in a ligand-independent manner is unknown. Given the structural diversity of AhR ligands, multiple mechanisms of AhR activation of gene expression, and species differences in AhR ligand binding and response, we examined the ability of 1,2-NQ and 1,4-NQ to bind to and activate the mouse and human AhRs using a series of in vitro AhR-specific bioassays and in silico modeling techniques. Both NQs induced AhR-dependent gene expression in mouse and human hepatoma cells, but were more potent and efficacious in human cells. 1,2-NQ and 1,4-NQ stimulated AhR transformation and DNA binding in vitro and was inhibited by AhR antagonists. Ligand binding analysis confirmed the ability of 1,2-NQ and 1,4-NQ to competitively bind to the AhR ligand binding cavity and the molecular determinants for interactions were predicted by molecular modeling methods. NQs were shown to bind distinctly differently from that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and differences were also observed between species. Mutation of amino acid residues (F289, M334, and M342) involved in critical NQ:AhR binding interactions, decreased NQ- and AhR-dependent gene expression, consistent with a role for these residues in binding and activation of the AhR by NQs. These studies provide insights into the molecular mechanism of action of NQs and contribute to the development of emerging NQ-based therapeutics.

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“…5. However, we found that 1,2-NQ also activates effector molecules such as the transcription factor arylhydrocarbon receptor (AhR), at least in part through covalent modifi cation to AhR, but not its regulator molecule heat shock protein 90, resulting in up-regulation of its downstream gene CYP1A1 (Abiko et al, 2015b(Abiko et al, , 2016. This suggests that S-arylation of an effector molecule is also involved in activation of the redox signal transduction pathway.…”

Section: Covalent Modifi Cation Of Proteins By 12-naphthoquinonementioning

confidence: 97%

Chemical toxicology of reactive species in the atmosphere: two decades of progress in an electron acceptor and an electrophile

2016

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Air pollutants such as diesel exhaust particles (DEP) are thought to cause pulmonary diseases such as asthma as a result of oxidative stress. While DEP contain a large number of polycyclic aromatic hydrocarbons, we have focused on 9,10-phenanthrenequinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ) because of their chemical properties based on their oxidative and chemical modification capabilities. We have found that 9,10-PQ interacts with electron donors such as NADPH (in the presence of enzymes) and dithiols, resulting in generation of excess reactive oxygen species (ROS) through redox cycling. We have also shown that 1,2-NQ is able to modify protein thiols, leading to protein adducts associated with activation of redox signal transduction pathways at lower concentrations and toxicity at higher concentrations. In this review, we briefly introduce our findings from the last two decades.

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Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator

Cited by 9 publications

References 25 publications

β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP+ Toxicity in Human Neuroblastoma SH-SY5Y Cells

β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP+ Toxicity in Human Neuroblastoma SH-SY5Y Cells

The Cellular and Molecular Determinants of Naphthoquinone-Dependent Activation of the Aryl Hydrocarbon Receptor

Chemical toxicology of reactive species in the atmosphere: two decades of progress in an electron acceptor and an electrophile

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