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Bromination Pattern of Hydroxylated Metabolites of BDE-47 Affects Their Potency to Release Calcium from Intracellular Stores in PC12 Cells
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
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2010 (Engelska)Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 118, nr 4, s. 519-525Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Brominated flame retardants, including the widely used polybrominated diphenyl ethers (PBDEs), have been detected in humans, raising concern about possible neurotoxicity. Recent research demonstrated that the hydroxylated metabolite 6-OH-BDE-47 increases neurotransmitter release by releasing calcium ions (Ca2+) from intracellular stores at much lower concentrations than its environmentally relevant parent congener BDE-47. Recently, several other hydroxylated BDE-47 metabolites, besides 6-OH-BDE-47, have been detected in human serum and cord blood. OBJECTIVE AND METHODS: To investigate the neurotoxic potential of other environmentally relevant PBDEs and their metabolites, we examined and compared the acute effects of BDE-47, BDE-49, BDE-99, BDE-100, BDE-153, and several metabolites of BDE-47-6-OH-BDE-47 (and its methoxylated analog 6-MeO-BDE-47), 6'-OH-BDE-49, 5-OH-BDE-47, 3-OH-BDE-47, and 4'-OH-BDE-49 on intracellular Ca2+ concentration ([Ca2+](i)), measured using the Ca2+-responsive dye Fura-2 in neuroendocrine pheochromocytoma (PC12) cells. RESULTS: In contrast to the parent PBDEs and 6-MeO-BDE-47, all hydroxylated metabolites induced Ca2+ release from intracellular stores, although with different lowest observed effect concentrations (LOECs). The major intracellular Ca2+ sources were either endoplasmic reticulum (ER; 5-OH-BDE-47 and 6'-OH-BDE-49) or both ER and mitochondria (6-OH-BDE-47, 3-OH-BDE-47, and 4'-OH-BDE-49). When investigating fluctuations in [Ca2+](i), which is a more subtle end point, we observed lower LOECs for 6-OH-BDE-47 and 4'-OH-BDE-49, as well as for BDE-47. CONCLUSIONS: The present findings demonstrate that hydroxylated metabolites of BDE-47 cause disturbance of the [Ca2+](i). Importantly, shielding of the OH group on both sides with bromine atoms and/or the ether bond to the other phenyl ring lowers the potency of hydroxylated PBDE metabolites.

Ort, förlag, år, upplaga, sidor
2010. Vol. 118, nr 4, s. 519-525
Nyckelord [en]
brominated flame retardant, calcium, calcium fluctuations, Fura-2, intracellular calcium stores, neurotoxicity, PC12, persistent organic pollutant, polybrominated diphenyl ether, structure-activity relationship
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materialkemi
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URN: urn:nbn:se:su:diva-50136DOI: 10.1289/ehp.0901339ISI: 000276454800025OAI: oai:DiVA.org:su-50136DiVA, id: diva2:380577
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authorCount :5Tillgänglig från: 2010-12-21 Skapad: 2010-12-21 Senast uppdaterad: 2022-02-28Bibliografiskt granskad

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Bergman, Åke

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