PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

Petriello, Michael C.; Han, Sung Gu; Newsome, Bradley J.; Hennig, Bernhard

doi:10.1016/j.taap.2014.03.018

Cited by 26 publications

(18 citation statements)

References 55 publications

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“…Moreover, it has been demonstrated that PCB exposure in animal models led to hepatic steatosis and non-alcoholic steatohepatitis in conjunction with a high fat diet (Wahlang et al 2013; Wahlang et al 2014b). Animal studies have also demonstrated that PCB exposure can lead to endothelial cell dysfunction and vascular inflammation (Petriello et al 2014). Moreover, NAFLD/NASH is considered as an independent CVD risk factor with defective heart-liver communication exacerbating CVD (Baskin et al 2014; Bhatia et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, based on the structure of the specific congener, PCBs have also been proposed to bind and/or activate different receptors in the body, eventually leading to different pathological outcomes (Wahlang et al 2014a). Animal studies have shown that coplanar PCB exposure is mostly associated with vascular cell dysfunction and inflammation (Petriello et al 2014) while exposure to higher chlorinated, non-coplanar PCBs is associated with obesity and fatty liver disease (Wahlang et al 2013; Wahlang et al 2014b). Humans are exposed to multiple PCB congeners especially the heavily-chlorinated ones that are more resistant to degradation and thus, tend to persist in the ecosystem.…”

Section: Introductionmentioning

confidence: 99%

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A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the PCB mixture, Arcolor1260 (20 mg/kg) and analyzed for inflammatory, calorimetry and metabolic parameters. Consistent with the literature, MCD diet-fed mice demonstrated steatosis, indicative of a compromised liver. Mice fed the MCD-diet and subsequently exposed to PCB126 showed observable wasting syndrome leading to mortality. PCB126 and Aroclor1260 exposure worsened hepatic fibrosis exhibited by the MCD groups. Interestingly, PCB126 but not Aroclor1260 induced steatosis and inflammation in CD-fed mice. Mice with liver injury and subsequently exposed to PCBs also manifested metabolic disturbances due to alterations in hepatic gene expression. Furthermore, PCB exposure in MCD-fed mice led to extra-hepatic toxicity such as upregulated circulating inflammatory biomarkers, implicating endothelial cell dysfunction. Taken together, these results indicate that environmental pollution can exacerbate toxicity caused by diet-induced liver injury which may be partially due to dysfunctional energy homeostasis. This is relevant to PCB-exposed human cohorts who suffer from alcohol or diet-induced fatty liver diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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“…Dysfunction of the endothelium is regarded as an important factor in the pathology of atherosclerosis [7]. There is accumulating evidence that persistent organic pollutants such as PCBs can accelerate an inflammatory response in vascular tissues [11–13, 22, 23, 41]. In the current studies, we demonstrated that EGCG significantly attenuated PCB 126-mediated induction of proatherogenic cytokines and adhesion molecules such as IL-6, CRP, ICAM-1, VCAM-1, and IL-1α/β in human endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells

Liu

Perkins

Hennig

2016

The Journal of Nutritional Biochemistry

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Anti-inflammatory polyphenols, such as epigallocatechin-3-gallate (EGCG), have been shown to protect against the toxicity of environmental pollutants. It is well known that bioactive food compounds such as polyphenols may exert their protection by modulating inflammatory pathways regulated through nuclear factor-kappa B (NF-κB) signaling. EGCG has been reported to inhibit NF-κB activation. We hypothesize that EGCG can protect against PCB-induced endothelial inflammation in part through epigenetic regulation of NF-kB-regulated inflammatory genes. In order to test this hypothesis, human endothelial cells (EA.hy926) were exposed to physiologically relevant levels of coplanar PCB 126 and/or 15 or 30 μM of EGCG, followed by quantification of NF-kB subunit p65, histone acetyltransferase (HAT) p300 and histone deacetylases (HDACs) accumulation through ChIP assay in the promotor region of inflammatory genes. In addition, the enrichment of the acetylated H3 (ac-H3) was also quantified. PCB 126 exposure increased the expression of vascular inflammatory mediators, including interleukin (IL)-6, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-1α/β, which were prevented by pre-treatment with EGCG. This inhibitory effect by EGCG correlated with abolished nuclear import of p65, decreased chromatin binding of p65 and p300, as well as increased chromatin binding of HDAC1/2. Furthermore, EGCG induced hypo-acetylation of H3, which accounts for deactivation of downstream genes. These data suggest that EGCG-induced epigenetic modifications can decrease PCB-induced vascular toxicity.

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“…For example, consumption of pro-inflammatory fatty acids such as linoleic and trans-fatty acids can contribute to endothelial cell dysfunction, a beginning stage of atherosclerosis (19, 20). Additionally, it has been demonstrated, primarily in experimental models, that exposure to environmental pollutants can cause endothelial cell dysfunction and chronic inflammation and may contribute to the development of CVDs (3, 28, 29). Furthermore, there is increasing experimental evidence that poor nutrition and pollutant exposure can interact and synergistically increase CVD risk (30).…”

Section: Nutrition As a Modulator Of Pollutant Toxicitymentioning

confidence: 99%

Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation

Hoffman

Petriello

Hennig

2017

Reviews on Environmental Health

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Abstract Exposure to environmental pollutants is a global health problem and is associated with the development of many chronic diseases, including cardiovascular disease, diabetes and metabolic syndrome. There is a growing body of evidence that nutrition can both positively and negatively modulate the toxic effects of pollutant exposure. Diets high in proinflammatory fats, such as linoleic acid, can exacerbate pollutant toxicity, whereas diets rich in bioactive and anti-inflammatory food components, including omega-3 fatty acids and polyphenols, can attenuate toxicant-associated inflammation. Previously, researchers have elucidated direct mechanisms of nutritional modulation, including alteration of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, but recently, increased focus has been given to the ways in which nutrition and pollutants affect epigenetics. Nutrition has been demonstrated to modulate epigenetic markers that have been linked either to increased disease risks or to protection against diseases. Overnutrition (i.e. obesity) and undernutrition (i.e. famine) have been observed to alter prenatal epigenetic tags that may increase the risk of offspring developing disease later in life. Conversely, bioactive food components, including curcumin, have been shown to alter epigenetic markers that suppress the activation of NF-κB, thus reducing inflammatory responses. Exposure to pollutants also alters epigenetic markers and may contribute to inflammation and disease. It has been demonstrated that pollutants, via epigenetic modulations, can increase the activation of NF-κB and upregulate microRNAs associated with inflammation, cardiac injury and oxidative damage. Importantly, recent evidence suggests that nutritional components, including epigallocatechin gallate (EGCG), can protect against pollutant-induced inflammation through epigenetic regulation of proinflammatory target genes of NF-κB. Further research is needed to better understand how nutrition can modulate pollutant toxicity through epigenetic regulation. Therefore, the objective of this review is to elucidate the current evidence linking epigenetic changes to pollutant-induced diseases and how this regulation may be modulated by nutrients allowing for the development of future personalized lifestyle interventions.

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PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

Cited by 26 publications

References 55 publications

A compromised liver alters polychlorinated biphenyl-mediated toxicity

A compromised liver alters polychlorinated biphenyl-mediated toxicity

EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells

Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation

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