Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells

Huc, Laurence; Lemarié, Anthony; Guéraud, Françoise; Héliès-Toussaint, Cécile

doi:10.1016/j.tiv.2012.03.017

Cited by 158 publications

(114 citation statements)

References 58 publications

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“…The brains were removed and postfixed in 4% paraformaldehyde for 24 h and then transferred to gradient of sucrose (10,20, and 30% in PBS). 30-m thin serial coronal sections covering the entire hippocampus were cut using a freezing microtome (Slee Mainz Co.).…”

Section: Methodsmentioning

confidence: 99%

“…BPA exposure causes abnormalities of liver function and hepatic damage associated with mitochondrial apoptosis (9). Further, low doses of BPA and exposure during maternal stage induced lipid accumulation and production of reactive oxygen species in the hepatic and testis mitochondria, respectively (10,11). Prenatal BPA exposure also impairs the mitochondria in the heart of neonatal rats (12).…”

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confidence: 99%

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Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

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The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU-and ␤-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPAmediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

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“…Also, Tsutsui et al (2000) examined the transforming and genotoxic activities of four types of bisphenols (BP-2, BP-3, BP-4, BP-5) in Syrian hamster embryo (SHE) cells and compared them with BPA; the most aneuploidogenic activity of bisphenol was BPA due to its chemical structure. Nakagawa and Tayama (2000) reported that BPA induced mitochondrial dysfunction, including a decrease in mitochondrial transmembrane potential and altered cellular oxidation-reduction in the isolated rat hepatocytes and in human HepG2 cell (Huc, Lemarie, Gueraud, & Helies-Toussaint, 2012), suggesting that mitochondria are a board of BPA at organelle level. It is recognized that mitochondria play a vital role in apoptosis by releasing the intermembrane space proteins, such as cytochrome c (Cyt c), which is a key mediator of apoptosis for activation of caspase in the cytosol (Kroemer, Galluzzi, & Brenner, 2007, Vaux, 2011.…”

Section: Introductionmentioning

confidence: 99%

The adverse effects of bisphenol A on male albino rats

Kamel

Foaud

Moussa

2018

JoBAZ

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Background: Bisphenol A (BPA) is a monomer used in the production of a multitude of chemical products, including epoxy resins and polycarbonates. The purpose of this study was to consider the biochemical, histological, genetic, and molecular alterations induced by BPA in adult male albino rats. They were orally subjected to BPA (20 and 100 mg/kg body weight) mixed in olive oil once a day for 30 days. At the end of the experiment, liver, testis, serum, and bone marrow were collected.

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“…Indeed, a recent epidemiological study has related BPA exposure to abnormal concentrations of the liver enzymes g-glutamyltransferase (gGT) and alkaline phosphatase (ALP), two of the sensitive markers for hepatocellular damage (Lang et al 2008). In addition, low concentrations of BPA (10 K4 -10 K12 M) have been reported to induce lipid accumulation and steatosis in hepatic HepG2 cells by disturbing mitochondrial function and releasing proinflammatory cytokines (Huc et al 2012). An animal study also confirmed that oral exposure of adult male CD1 mice to BPA (0, 5, 50, 500, and 5000 mg/kg per day) resulted in the accumulation of hepatic triglycerides (TGs) and cholesteryl esters (CHOL), changes in hepatic free fatty acid (FFA) composition as well as upregulation of genes involved in lipid biosynthesis (Marmugi et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Jie¹,

Sun²,

Chen³

et al. 2014

Journal of Endocrinology

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Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 mg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population.

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Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells

Cited by 158 publications

References 58 publications

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

The adverse effects of bisphenol A on male albino rats

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

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