Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

Al-Salman, Fadheela.; Plant, Nick

doi:10.1016/j.taap.2012.05.016

Cited by 83 publications

(53 citation statements)

References 41 publications

(39 reference statements)

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“…Indeed, there are reports that several non-coplanar PCBs (rather than the coplanar PCBs known to be highly toxic) directly activate CAR and PXR and increase transcription of genes for CYP2B and CYP3A (Al-Salman and Plant, 2012;Gährs et al, 2013). However, the CAR/PXR agonistic properties of PCBs are a new subject for investigation and it is not known how metabolism of PCBs changes their abilities to interact with the CAR/PXR.…”

Section: Introductionmentioning

confidence: 99%

Detection and measurement of the agonistic activities of PCBs and mono-hydroxylated PCBs to the constitutive androstane receptor using a recombinant yeast assay

Kamata

Shiraishi

Kageyama

et al. 2015

Toxicology in Vitro

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Section: Introductionmentioning

confidence: 99%

Detection and measurement of the agonistic activities of PCBs and mono-hydroxylated PCBs to the constitutive androstane receptor using a recombinant yeast assay

Kamata

Shiraishi

Kageyama

et al. 2015

Toxicology in Vitro

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“…However, treatment with PXR agonist in a transgenic mouse model expressing human apoE and CETP, designed to mimic human lipoprotein metabolism, decreased HDL-C indicating a shuttling of cholesterol to apoB-containing lipoproteins [de Haan et al 2009]. There also appears to be a species difference since PCBs can act as both agonists and antagonists, depending on the concentration, in cells expressing human PXR but not the rat or mouse PXR [Al-Salman andPlant 2012, Tabb et al 2004]. …”

Section: Effects Of Popsmentioning

confidence: 99%

Lipoproteomics Environmental and Genetic Factors Affecting High-Density Lipoprotein (HDL)

Ljunggren¹

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Lipoprotein particles act as lipid transporters in the blood stream, and measuring cholesterol content in specific subclasses of lipoprotein particles has long been, and still is, a frequently used tool to estimate the risk of cardiovascular disease (CVD). High-density lipoprotein (HDL) is a subclass of lipoproteins often regarded as providing protection against CVD via several functions including reverse cholesterol transport and antiinflammatory capacities. However, the precise relationship between HDL cholesterol levels and health outcome is still unclear. Lately, new approaches to study HDL composition and function have therefore become more important.HDL function is to a large extent dependent on its proteome, containing more than 100 proteins. Investigating the proteome in individuals with altered gene expression for HDLassociated proteins or with known exposure to environmental contaminants may reveal new insights into how HDL metabolism is affected by various factors. This is of interest in order to better understand the role of HDL in CVD.Papers I and II focus on two different mutations in a structural HDL protein, apolipoprotein A-I (L202P and K131del), and one mutation in the scavenger receptor class B-1 (P297S), which is involved in selective lipid uptake of cholesterol mainly into hepatocytes and adrenal cells. The HDL proteome was analyzed using two-dimensional gel electrophoresis and mass spectrometry. The L202P mutation was identified in HDL of the heterozygote carriers together with a significant decrease of apolipoprotein E and increased zinc-alpha-2-glycoprotein. By contrast, the second apolipoprotein A-I mutation (K131del) was associated with significantly elevated alpha-1-antitrypsin and transthyretin levels. Protein analyses of the scavenger receptor class B1 P297S heterozygotes showed a significant increase in HDL apoL-1 along with increased free apoE. The carriers showed no difference in anti-oxidative capability but a significant increase in apoA-I methionine oxidation.Papers III and IV focus on persistent organic pollutants that may influence HDL composition and function. These compounds accumulate in humans, and exposure has been linked to an increased risk of CVD. To provide a better understanding of the HDL system in relation to pollutants, a population living in a contaminated area was studied. Persistent organic pollutants in isolated HDL were quantified using high-resolution gas chromatography mass spectrometry and significantly increased levels were found in individuals with CVD as compared to healthy controls. Furthermore, there was a significant negative association between the pollutants and paraoxonase-1 anti-oxidant activity. Studying the proteome with nano-liquid chromatography tandem mass ii spectrometry led to the identification of 118 proteins in HDL, of which ten were significantly associated with the persistent organic pollutants. In summary, the present studies demonstrate protein pattern alterations in HDL associated with inherited genetic variants or polluta...

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“…Recent studies have demonstrated PCBs' interaction with other nuclear receptors including human PXR and rodent peroxisome-proliferator activated receptor alpha (PPARα) (97)(98)(99). We hypothesized that Aroclor 1260 may interact with these receptors in our animal model.…”

Section: Aroclor 1260 Induced Hepatic Car Pxr and Ahr Target Genesmentioning

confidence: 99%

Evaluating the effects of aroclor 1260 in non-alcoholic fatty liver disease : the role of xenobiotic receptors.

Wahlang¹

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Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

Cited by 83 publications

References 41 publications

Detection and measurement of the agonistic activities of PCBs and mono-hydroxylated PCBs to the constitutive androstane receptor using a recombinant yeast assay

Detection and measurement of the agonistic activities of PCBs and mono-hydroxylated PCBs to the constitutive androstane receptor using a recombinant yeast assay

Lipoproteomics Environmental and Genetic Factors Affecting High-Density Lipoprotein (HDL)

Evaluating the effects of aroclor 1260 in non-alcoholic fatty liver disease : the role of xenobiotic receptors.

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