Vitamin D Receptor Activation Enhances Benzo[<i>a</i>]pyrene Metabolism via CYP1A1 Expression in Macrophages

Matsunawa, Manabu; Akagi, Daisuke; Uno, Shigeyuki; Endo-Umeda, Kaori; Yamada, Sachiko; Ikeda, Kazumasa; Makishima, Makoto

doi:10.1124/dmd.112.046839

Cited by 34 publications

(20 citation statements)

References 49 publications

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“…Thus, the combination of PAH and 1,25 (OH) 2 D 3 both enhances B[a]P metabolism and 1,25 (OH) 2 D 3 catabolism through CYP1A1 and CYP24A1, respectively (Matsunawa et al . ). A negative correlation between organic contaminant exposure and VD status has been shown in several mammalian species (Routti et al .…”

Section: Pah Interactions With Vitaminsmentioning

confidence: 97%

“…Potential reactive phase I intermediate PAH metabolites are further metabolized in second phase (II) reactions that are catalysed by enzymes such as glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs) and 3 0 -phospho-5 0adenylyl sulphate sulfotransferase, which have several biological functions including the conjugation of the reactive toxicant intermediates to, respectively, glutathione (GSH), glucuronides and sulphates (Schlenk et al 2008). There are at least eighteen CYP families in all fish species, and although four CYP (CYP1, CYP2, CYP3 and CYP4) families are induced and/or metabolized by xenobiotica (Uno et al 2012), the CYP1 family isozymes in fish are best known for oxidative metabolization and phase I detoxification of environmental contaminants. The CYP1A1-catalysed EROD activity is one of the most well-known contaminant oxidation mechanisms and used as an indicator for toxicant exposure in several tissues Beijer et al 2013).…”

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confidence: 99%

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Polyaromatic hydrocarbons in aquafeeds, source, effects and potential implications for vitamin status of farmed fish species: a review

Berntssen¹,

Ørnsrud²,

Hamre³

et al. 2015

Aquacult Nutr

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Access to marine feed ingredients is considered a limiting factor for the rapidly growing aquaculture industry. With increasing inclusion of vegetable feed ingredients in aquafeeds, new challenges have arisen. Substituting marine oils and meals with vegetable ingredients has decreased the level of persistent organic pollutants (POPs) in marine farmed fish such as Atlantic salmon. Consequently, this shift in feed ingredients has led to increased levels of polyaromatic hydrocarbons (PAHs) in aquafeeds. Several of the PAHs listed are on EFSAs and EPAs list of priority substances. Not only are the carcinogenic and genotoxic properties of PAHs of concern, but also their ability to interact with and disrupt metabolic pathways such as vitamin metabolism and signalling. The interactions, and the potential depletion of vitamin stores that follows, are of particular interest as marine ingredients are naturally rich in micronutrients such as vitamins A and D. This study has summarized the current knowledge on the effect of PAHs commonly found in vegetable feed ingredients on vitamin metabolism/signalling and their possible implications in fish.

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Section: Pah Interactions With Vitaminsmentioning

confidence: 97%

mentioning

confidence: 99%

Polyaromatic hydrocarbons in aquafeeds, source, effects and potential implications for vitamin status of farmed fish species: a review

Berntssen¹,

Ørnsrud²,

Hamre³

et al. 2015

Aquacult Nutr

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“…7 VDR is part of superfamily of nuclear receptors and responsible for the regulations of genes involved in calcium homeostasis, cell proliferation, and cell differentiation. VDR also regulates the expression of p450 enzymes such as CYP24A1 8 and CYP27B1 9 as part of its ligand autoregulation and CYP3A4 , 10 CYP19A1 11 and CYP1A1 12 as a xenobiotic sensor similar to the pregnane X receptor (PXR) and constitutive androstane receptor (CAR). 13 This article summarizes the discoveries around the “final” metabolite of vitamin D, calcitroic acid.…”

Section: Introductionmentioning

confidence: 99%

Calcitroic Acid–A Review

Arnold

2016

ACS Chem. Biol.

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Calcitroic acid was isolated and characterized almost four decades ago but little is known about this important vitamin D metabolite. Four reported synthetic strategies to generate calcitroic acid are presented that highlight the scientific progress in the field of chemistry directed to vitamin D analog synthesis. The most recent synthesis described the generation of calcitroic acid with an overall yield of 12.8% in 13 steps. The endogenous formation of calcitroic acid has been demonstrated in perfused rat kidney using 24,25,26,27-tetranor-1,23(OH)2D3. Although, the majority of vitamin D metabolism is mediated by 24-hydoxylase (CYP24A1), it is not clear why the formation of calcitroic acid was not observed in the presence of recombinant CYP24A1 enzyme. Furthermore, it is not known if enzyme 1α-hydroxylase (CYP27B1) can convert calcioic acid into calcitroic acid. In addition to the lack of research investigating the endogenous formation of calcitroic acid the physiological role of calcitroic acid remains unknown. Only a few reports mentioned the biological activity of calcitroic acid in connection with the vitamin D receptor (VDR). When administered subcutaneous, calcitroic acid has anthracitic properties and elevates calcium blood levels when administered i.v.. In vitro, calcitroic acid at higher concentrations has been shown to bind VDR and induce gene transcription. However, these studies were not carried out in cells derived from target organs of calcitroic acid such as kidney, liver, and intestine. We can conclude that our current knowledge of calcitroic acid is limited and more studies are needed to identify its physiological role.

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“…In HCT116 colon cancer cells, however, ADTT induced recruitment of RXR and surprisingly SMRT to the DNA-bound VDR. In THP-1 cells, ADTT and ADMI3 reduced the mRNA levels of CYP1A1 in the presence of 1,25-(OH) 2 D 3 and benzo[a]pyrene (an aryl hydrocarbon agonist) (156). A recent series of ADTK1-4 analogs exhibited significantly less antagonist activity than ADTT (157).…”

Section: Vdr Antagonists or Allosteric Inhibition Of The Vdr–coregmentioning

confidence: 99%

Inhibitors for the Vitamin D Receptor–Coregulator Interaction

Teske

2016

Vitamin D Hormone

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The vitamin D receptor (VDR) belongs to the superfamily of nuclear receptors and is activated by the endogenous ligand 1,25-dihydroxyvitamin D3. The genomic effects mediated by VDR consist of the activation and repression of gene transcription, which includes the formation of multi-protein complexes with coregulator proteins. Coregulators bind many nuclear receptors and can be categorized according their role as coactivators (gene activation) or corepressors (gene repression). Herein, different approaches to develop compounds that modulate the interaction between VDR and coregulators are summarized. This include coregulator peptides that were identified by creating phage display libraries. Subsequent modification of these peptides including the introduction of a tether or non-hydrolysable bonds resulted in the first direct VDR–coregulator inhibitors. Later, small molecules that inhibit VDR–coregulator inhibitors were identified using rational drug design and high throughput screening. Early on, allosteric inhibition of VDR–coregulator interactions was achieved with VDR antagonists that change the conformation of VDR and modulate the interactions with coregulators. A detailed discussion of their dual agonist/antagonist effects is given as well as a summary of their biological effects in cell-based assays and in vivo studies.

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Vitamin D Receptor Activation Enhances Benzo[a]pyrene Metabolism via CYP1A1 Expression in Macrophages

Cited by 34 publications

References 49 publications

Polyaromatic hydrocarbons in aquafeeds, source, effects and potential implications for vitamin status of farmed fish species: a review

Polyaromatic hydrocarbons in aquafeeds, source, effects and potential implications for vitamin status of farmed fish species: a review

Calcitroic Acid–A Review

Inhibitors for the Vitamin D Receptor–Coregulator Interaction

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