期刊
REPRODUCTIVE TOXICOLOGY
卷 33, 期 1, 页码 67-75出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2011.11.004
关键词
Benzyl butyl phthalate; Human granulosa cell; Aryl hydrocarbon receptor; Cytochrome P450 1B1; Necrosis
资金
- National Science Council, Taiwan [NSC 97-2314-B-037-010-MY3, NSC-99-2628-B-037-009-MY3]
- Ministry of Education, Taiwan [KMU-EM-99-3]
- Kaohsiung Medical University Research Foundation [KMUER 004]
- Kaohsiung Medical University Hospital [KMUH 98-8R19, KMUH-99-9I04]
We investigated the signaling pathway of the arylhydrocarbon receptor (AhR) on HO23 cells (immortalized human granulosa cells (hGC)) mediated by benzyl butyl-phthalate (BBP). BBP (1 mu M) significantly increased the mRNA and protein levels of AhR, aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome-P450 (CYP)1B1 in HO23 cells. Treatment with 3',4'-dimethoxyflavone (3',4'-DMF) or AhR siRNA significantly reduced AhR and CYP1B1, but CYP1A1 was not affected by 3',4'-DMF or AhR siRNA, suggesting that increases in CYP1A1 may not regulated by AhR. BBP induced the AhR fusion protein to localize and accumulate around the nucleus, and AhR heterodimerization with ARNT was observed in the nucleus by immunoprecipitation. Chromatin immunoprecipitation and reporter assays revealed the effect of BBP on CYP1B1, but not CYP1A1. Necrosis was significantly increased in HO23 cells after BBP treatment, and 3',4'-DMF,AhR siRNA or CYP1B1 siRNA knockdown blocked this phenomenon. These data suggest that BBP-induced HO23 cell necrosis is AhR and CYP1B1 dependent. (C) 2011 Elsevier Inc. All rights reserved.
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