1,2,5,6,9,10-αHexabromocyclododecane (HBCD) impairs thyroid hormone-induced dendrite arborization of Purkinje cells and suppresses thyroid hormone receptor-mediated transcription

Ibhazehiebo, K; Iwasaki, T; Shimokawa, N; Koibuchi, N

HERO ID

1402779

Reference Type

Journal Article

Year

2011

Language

English

PMID

20967578

HERO ID 1402779
In Press No
Year 2011
Title 1,2,5,6,9,10-αHexabromocyclododecane (HBCD) impairs thyroid hormone-induced dendrite arborization of Purkinje cells and suppresses thyroid hormone receptor-mediated transcription
Authors Ibhazehiebo, K; Iwasaki, T; Shimokawa, N; Koibuchi, N
Journal Cerebellum
Volume 10
Issue 1
Page Numbers 22-31
Abstract 1,2,5,6,9,10-αHexabromocyclododecane (HBCD) is a nonaromatic, brominated cyclic alkane used as an additive flame retardant. It bioaccumulates, persists in the environment, and has been detected in humans and wildlife. Its developmental neurotoxicity is of great concern. We investigated the effect of HBCD on thyroid hormone (TH) receptor (TR)-mediated transcription using transient transfection-based reporter gene assays and found that a low-dose (10(-10) M) HBCD suppressed TR-mediated transcription. We further examined the effect of HBCD on interaction of TR with TH response element (TRE) and found a partial dissociation of TR from TRE. HBCD did not dissociate steroid receptor coactivator-1 from TR in the presence of TH; neither did it recruit corepressors (N-CoR and SMRT) to TR in the absence of TH. Furthermore, low-dose HBCD (10(-10) M) significantly suppressed TH-induced dendrite arborization of Purkinje cells in primary cerebellar culture derived from newborn rat. These results show that low-dose HBCD can potentially disrupt TR-mediated transactivation and impairs Purkinje cell dendritogenesis, suggesting that HBCD can interfere with TH action in target organs, including the developing brain.
Doi 10.1007/s12311-010-0218-1
Pmid 20967578
Wosid WOS:000287330600004
Is Certified Translation No
Dupe Override No
Comments Journal: ISSN:
Is Public Yes
Language Text English
Keyword HBCD; Thyroid hormone; Thyroid hormone response element (TRE); Purkinje cells; Thyroid hormone receptor; Transcriptional regulation
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