Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2568473 | Toxicology and Applied Pharmacology | 2014 | 11 Pages |
Abstract
Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation.
Keywords
GCLMBDE-47PBDEsEVTGSRBSOHeme oxygenase-1TrxPtgs2HMOX1NQO1DHCR24GPx1FHL2b2mNF-κBPRNPHTR-8/SVneo cellsSQSTM1sequestosome 1AOX1FTH1Nuclear factor E2-related factor 2 (Nrf2)SLC7A11IUGRTxnrd1NAD(P)H dehydrogenase, quinone 1sulfiredoxin 1four and a half LIM domains 2SRXN1GSHPGE2FBSGSTTBHQCOX-2NACHO-1Nrf224-dehydrocholesterol reductasekeap1DMSON-acetylcysteineROSaldehyde oxidase 1Polybrominated diphenyl ethers (PBDEs)interleukinbuthionine sulfoximinetert-butyl hydroquinoneextravillous trophoblastThioredoxin reductase 1ELISAEnzyme-linked immunosorbent assaythioredoxinPolybrominated diphenyl ethersDimethyl sulfoxidefetal bovine serumCMVcytomegalovirusCytokinesCyclooxygenase-2nuclear factor E2-related factor 2antioxidant response elementnuclear factor kappa Bglutamate-cysteine ligase, modifier subunitintrauterine growth restrictionAREheme oxygenase (decycling) 1Antioxidant responseKelch-like ECH-associated protein 1Prion proteinProstaglandin E2prostaglandin-endoperoxide synthase 2Glutathioneglutathione S-transferaseglutathione reductaseglutathione peroxidase 1Reactive oxygen species
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Authors
Hae-Ryung Park, Rita Loch-Caruso,