Abstract:
BACKGROUND:Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants and are becoming a ubiquitous environmental contaminant. Adverse effects in the developing brain are of great health concern. OBJECTIVE:We investigated the effect of PBDEs/hydroxylated PBDEs (OH-PBDEs) on thyroid hormone (TH) receptor (TR)-mediated transcription and on TH-induced dendrite arborization of cerebellar Purkinje cells. METHODS:We examined the effect of PBDEs/OH-PBDEs on TR action using a transient transfection-based reporter gene assay. TR-cofactor binding was studied by the mammalian two-hybrid assay, and TR-DNA [TH response element (TRE)] binding was examined by the liquid chemiluminescent DNA pull-down assay. Chimeric receptors generated from TR and glucocorticoid receptor (GR) were used to identify the functional domain of TR responsible for PBDE action. The change in dendrite arborization of the Purkinje cell in primary culture of newborn rat cerebellum was also examined. RESULTS:Several PBDE congeners suppressed TR-mediated transcription. The magnitude of suppression correlated with that of TR-TRE dissociation. PBDEs suppressed transcription of chimeric receptors containing the TR DNA binding domain (TR-DBD). We observed no such suppression with chimeras containing GR-DBD. In the cerebellar culture, PBDE significantly suppressed TH-induced Purkinje cell dendrite arborization. CONCLUSIONS:Several PBDE congeners may disrupt the TH system by partial dissociation of TR from TRE acting through TR-DBD and, consequently, may disrupt normal brain development.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Ibhazehiebo K,Iwasaki T,Kimura-Kuroda J,Miyazaki W,Shimokawa N,Koibuchi Ndoi
10.1289/ehp.1002065subject
Has Abstractpub_date
2011-02-01 00:00:00pages
168-75issue
2eissn
0091-6765issn
1552-9924journal_volume
119pub_type
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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更新日期:1995-11-01 00:00:00
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更新日期:2019-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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更新日期:1995-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
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更新日期:1985-05-01 00:00:00
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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