PMID- 31767456 OWN - NLM STAT- MEDLINE DCOM- 20200320 LR - 20210816 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 189 DP - 2020 Feb TI - The steroid receptor coactivator 1 (SRC1) and 3 (SRC3) recruitment as a novel molecular initiating event of 4-n-nonylphenol in estrogen receptor alpha-mediated pathways. PG - 109958 LID - S0147-6513(19)31289-8 [pii] LID - 10.1016/j.ecoenv.2019.109958 [doi] AB - Recently, the action of steroid receptor coactivators (SRCs) has been recognized to be an important molecular initiating event (MIE) in estrogenic adverse outcome pathways (AOPs). However, the role of SRCs in the molecular mechanisms of many highly concerned environmental estrogens remains poorly understood. In this study, the widely studied environmental estrogen, 4-n-nonylphenol (4-n-NP), was used as a typical pollutant to study SRCs recruitment in its estrogenic effects. In MCF7 cell proliferation (E-SCREEN) assay and MVLN cell assay, 4-n-NP showed significant estrogenic potency that involved an increase in estrogen receptor alpha (ERalpha), SRC1 and SRC3 transcript levels. Moreover, 4-n-NP was found to induce estrogen response element (ERE)-mediated activity via ERalpha in MVLN cells. To investigate the mechanism by which SRCs recruitment is induced by 4-n-NP-ERalpha, a coactivators recruitment assay was performed, and the results showed that 4-n-NP-ERalpha recruited both SRC1 and SRC3, whereas it failed to recruit SRC2. Similarly, it had no interaction with SRC2 in the ERalpha-SRC2 two-hybrid yeast assay. This is the first report to investigate the novel MIE of SRCs recruitment in 4-n-NP-ERalpha-induced estrogenicity. Overall, our results suggest that the action of 4-n-NP on estrogenic effects involves the following MIEs: the activation of ERalpha, the recruitment of SRC1 and SRC3, and the induction of ERE-mediated activity. The findings also provide valuable insights into the MIE associated with the different SRCs that are recruited in the adverse outcome pathways of environmental estrogens. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Ji, Xiaoya AU - Ji X AD - Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Li, Na AU - Li N AD - Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Yang, Rong AU - Yang R AD - Beijing Water Quality Monitoring Center for South-to-North Water Diversion, Beijing, 100093, China. FAU - Rao, Kaifeng AU - Rao K AD - Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China. FAU - Ma, Mei AU - Ma M AD - Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: mamei@rcees.ac.cn. FAU - Wang, Zijian AU - Wang Z AD - Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China. LA - eng PT - Journal Article DEP - 20191122 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (ESR1 protein, human) RN - 0 (Environmental Pollutants) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 0 (Phenols) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (NCOA3 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 3) RN - I03GBV4WEL (4-nonylphenol) SB - IM MH - Cell Proliferation/drug effects MH - Environmental Pollutants/*pharmacology MH - Estrogen Receptor alpha/*metabolism MH - Estrogens/*pharmacology MH - Humans MH - MCF-7 Cells MH - Nuclear Receptor Coactivator 1/*metabolism MH - Nuclear Receptor Coactivator 3/*metabolism MH - Phenols/*pharmacology OTO - NOTNLM OT - 4-n-Nonylphenol OT - Estrogen receptor alpha (ERalpha) OT - Estrogenic activity OT - Molecular initiating event (MIE) OT - Steroid receptor coactivator (SRC) EDAT- 2019/11/27 06:00 MHDA- 2020/03/21 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/09/26 00:00 [received] PHST- 2019/11/10 00:00 [revised] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/03/21 06:00 [medline] PHST- 2019/11/27 06:00 [entrez] AID - S0147-6513(19)31289-8 [pii] AID - 10.1016/j.ecoenv.2019.109958 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2020 Feb;189:109958. doi: 10.1016/j.ecoenv.2019.109958. Epub 2019 Nov 22.