High-throughput evaluation of aryl hydrocarbon receptor-binding sites selected via chromatin immunoprecipitation-based screening in Hepa-1c1c7 cells stimulated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Kinehara, Masaki; Fukuda, Itsuko; Yoshida, Kenichi; Ashida, Hitoshi

doi:10.1266/ggs.83.455

Cited by 15 publications

(20 citation statements)

References 56 publications

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“…The COX-2/PGE 2 pathway is also implicated in the pathogenesis of dioxin-induced hydronephrosis ( 164 ). The toxic effects of dioxins are mediated by the arylhydrocarbon receptor, which binds to the second intron of Pla2g4a and mediates its induction ( 165,166 ). The arylhydrocarbon receptor pathway also promotes signaling cascades for posttranslational activation of cPLA 2 ␣ by increasing calcium and phosphorylation ( 167,168 ).…”

Section: Reproductionmentioning

confidence: 99%

Cytosolic phospholipase A2: physiological function and role in disease

Leslie

2015

Journal of Lipid Research

349

257

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Section: Reproductionmentioning

confidence: 99%

Cytosolic phospholipase A2: physiological function and role in disease

Leslie

2015

Journal of Lipid Research

349

257

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“…Hypoxia Inducible Factor 1α (HIF1α) or AhR repressor (AHRR)), and differences in chromatin structure and epigenetic modifications of AhR target genes [4,12,16–19]. AhR-dependent alterations in the expression of genes that lack an apparent AhR DNA (DRE) binding site, coupled with established cross-talk between the AhR and cellular signaling pathways and other transcription factors, suggests that the AhR participates in several novel noncannonical pathways by which the AhR can stimulate gene expression [6,20–23]. Ligand-activated AhR can dimerize with nuclear proteins other than ARNT (e.g., Kruppel-like factor 6 (KLF6) and RelB), and these unique heterodimers stimulate gene expression via their interaction with DNA binding sites that are significantly different from that of a DRE [24–28] to regulate a unique set of genes (Figure 1).…”

Section: Diversity In Ahr-dependent Mechanisms Of Gene Expressionmentioning

confidence: 99%

And now for something completely different: Diversity in ligand-dependent activation of Ah receptor responses

Denison

Faber

2017

Current Opinion in Toxicology

104

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Ligand-dependent activation of the Ah receptor (AhR) can result in an extremely diverse spectrum of biological and toxic effects that occur in a ligand-, species- and tissue-specific manner. While the classical mechanism of AhR-dependent signal transduction is directly related to its ability to modulate gene expression, the dramatic diversity in responses observed following AhR activation or inhibition is inconsistent with a single molecular mechanism of AhR action. Recent studies have revealed that key molecular events underlying the AhR signaling pathway are significantly more varied and complex than previously established, and the specificity and diversity in AhR response can be selectively modulated by a variety of factors. Here we describe new insights into the mechanistic diversity in AhR signal transduction that can contribute to ligand-, species- and tissue-specific differences in AhR reponse.

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“…However, it cannot be ruled out that early increase in [Ca 2+ ] i levels also contribute to the toxic effects caused by TCDD. An early increase in [Ca 2+ ] i levels results in activation of phospholipase A2 with subsequent release of arachidonic acid (AA, n6 fatty acid) from membrane phospholipids (Kita et al 2006;Kinehara et al 2009;Kopec et al 2010). The released arachidonic acid acts as a substrate for COX-2 and cytochrome P450s and results in the production of pro-inflammatory eicosanoids (Bui et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Palaniswamy

Vishwanadha

Singaravelu

2014

Cell Stress and Chaperones

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Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDDinduced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDDinduced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na + -K + and Mg 2+ATPases activities with increase in Ca 2+ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.

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High-throughput evaluation of aryl hydrocarbon receptor-binding sites selected via chromatin immunoprecipitation-based screening in Hepa-1c1c7 cells stimulated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Cited by 15 publications

References 56 publications

Cytosolic phospholipase A2: physiological function and role in disease

Cytosolic phospholipase A2: physiological function and role in disease

And now for something completely different: Diversity in ligand-dependent activation of Ah receptor responses

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

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