2010年9月
Endocrine disrupting chemicals bind to a novel receptor, microtubule-associated protein 2, and positively and negatively regulate dendritic outgrowth in hippocampal neurons
JOURNAL OF NEUROCHEMISTRY
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- 巻
- 114
- 号
- 5
- 開始ページ
- 1333
- 終了ページ
- 1343
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1471-4159.2010.06847.x
- 出版者・発行元
- WILEY-BLACKWELL
P>The present study demonstrates a novel high-affinity neuronal target for endocrine disrupting chemicals (EDCs), which potentially cause psychological disorders. EDCs competitively inhibited the binding of bovine serum albumin-conjugated progesterone to recombinant human microtubule-associated protein 2C (rhMAP2C) with an inhibition constant at picomolar levels. In the rhMAP2C-stimulated tubulin assembly assay, agonistic enhancement was observed with dibutyl phthalate and pentachlorphenol and pregnenolone, while an inverse agonistic effect was observed with 4-nonylphenol. In contrast, progesterone and many of the EDCs, including bisphenol A, antagonized the pregnenolone-induced enhancement of rhMAP2C-stimulated tubulin assembly. These agonistic and inverse agonistic actions were not observed in tubulin assembly stimulated with delta 1-71 rhMAP2C, which lacks the steroid-binding site. Using a dark-field microscopy, pregnenolone and pentachlorphenol were observed to generate characteristic filamentous microtubules in a progesterone- or bisphenol A-reversible manner. In cultured hippocampal neurons, similar agonist-antagonist relationships were reproduced in terms of dendritic outgrowth. Fluorescent recovery after photobleaching of hippocampal neurons showed that pregnenolone and agonistic EDCs enhanced, but that 4-nonylphenol inhibited the MAP2-mediated neurite outgrowth in a progesterone- or antagonistic EDC-reversible manner. Furthermore, none of the examined effects were affected by mifepristone or ICI-182,786 i.e. the classical progesterone and estrogen receptor antagonists. Taken together, these results suggest that EDCs cause a wide variety of significant disturbances to dendritic outgrowth in hippocampal neurons, which may lead to psychological disorders following chronic exposure during early neuronal development.
- リンク情報
- ID情報
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- DOI : 10.1111/j.1471-4159.2010.06847.x
- ISSN : 0022-3042
- PubMed ID : 20534002
- Web of Science ID : WOS:000280644000008