Disruption of thyroid hormone receptor-mediated transcription and thyroid hormone-induced Purkinje cell dendrite arborization by polybrominated diphenyl ethers.
Disruption of thyroid hormone receptor-mediated transcription and thyroid hormone-induced Purkinje cell dendrite arborization by polybrominated diphenyl ethers.
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DOI：
10.1289/ehp.1002065
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发表时间：
2011-02
影响因子：
10.4
通讯作者：
Koibuchi N
中科院分区：
文献类型：
--
作者：
Ibhazehiebo K;Iwasaki T;Kimura-Kuroda J;Miyazaki W;Shimokawa N;Koibuchi N
多溴联苯醚(PBDEs)已被用作阻燃剂，成为一种普遍存在的环境污染物。对发育中的大脑的不利影响是极大的健康问题。我们研究了PBDEs/羟化PBDEs(OH-PBDEs)对甲状腺激素受体(TH)介导的转录和TH诱导的小脑浦肯野细胞树突状分枝的影响。我们使用基于瞬时转染的报告基因检测了PBDEs/OH-PBDEs对转录激活剂作用的影响。用哺乳动物双杂交实验研究了TR型辅因子的结合，用液体化学发光DNA下拉实验检测了TR型DNA[TH反应元件(TrE)]的结合。利用TRR和糖皮质激素受体(GR)产生的嵌合受体来确定负责PBDE作用的TRR的功能结构域。此外，还观察了新生大鼠小脑原代培养中浦肯野细胞树突分支的变化。几种多溴二苯醚的同系物抑制了tr介导的转录。抑制的程度与tr-tre解离的程度相关。PBDEs抑制含有TRDNA结合域(TRDBD)的嵌合受体的转录。我们在含有GR-DBD的嵌合体中没有观察到这种抑制。在小脑培养中，PBDE显著抑制TH诱导的浦肯野细胞树突状分枝。几种多溴二苯醚的同系物可能通过部分解离tr和tre，通过tr-DBD作用于TH系统，从而可能扰乱正常的大脑发育。
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. 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. 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. 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. 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.
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影响因子：
3.3
作者：
Londono, Marina;Shimokawa, Noriaki;Koibuchi, Noriyuki
通讯作者：
Koibuchi, Noriyuki
影响因子：
5.6
作者：
CAREY, M;KAKIDANI, H;PTASHNE, M
通讯作者：
PTASHNE, M
影响因子：
4.8
作者：
Koibuchi, N;Liu, Y;Chin, WW
通讯作者：
Chin, WW
影响因子：
3.8
作者：
Dingemans, Milou M. L.;van den Berg, Martin;Westerink, Remco H. S.
通讯作者：
Westerink, Remco H. S.
影响因子：
10.4
作者：
Kojima H;Takeuchi S;Uramaru N;Sugihara K;Yoshida T;Kitamura S
通讯作者：
Kitamura S