Yum Soomin, Lee Haksoo, Kwon Yong-Kook, Lee Gunyoung, Lee Hye-Young, Youn HyeSook, Youn BuHyun
Department of Integrated Biological Science, Pusan National University, Kumjeong-ku, Republic of Korea.
Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Cheongju-si, Republic of Korea.
Anim Cells Syst (Seoul). 2025 Apr 28;29(1):282-295. doi: 10.1080/19768354.2025.2481984. eCollection 2025.
Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interact with the estrogen receptor (ER), thereby disrupting estrogen-mediated signaling. In a previous study, we employed a bioluminescence resonance energy transfer (BRET) system to assess ER dimerization for detecting EDCs. To further determine whether the BRET assay could be used independently to identify EDCs, we investigated ER-EDC interactions before and after dimerization. Results from isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) revealed that ER dimerization can be mediated by EDCs. Consequently, the BRET assay proved effective in detecting dimerization and clarifying its relevance to EDC-induced signaling disruption. Additionally, to examine EDC-induced transcriptional changes, we performed chromatin immunoprecipitation sequencing (ChIP-seq), followed by gene ontology (GO) analysis. These analyses demonstrated that EDCs affect various signaling pathways, including those involved in antibody-dependent cytotoxicity, bone morphogenetic protein (BMP) signaling in cardiac induction, and hepatocyte growth factor receptor signaling. Overall, this study elucidates the molecular mechanisms by which EDCs influence ER dimerization and signaling. These findings highlight the utility of the BRET-based assay for EDC detection and contribute to a deeper understanding of the systemic effects of EDCs on endocrine disruption.
内分泌干扰化学物质（EDCs）是与雌激素受体（ER）相互作用的外源性化合物，从而扰乱雌激素介导的信号传导。在先前的一项研究中，我们采用生物发光共振能量转移（BRET）系统来评估ER二聚化以检测EDCs。为了进一步确定BRET测定法是否可独立用于鉴定EDCs，我们研究了二聚化前后的ER-EDC相互作用。等温滴定量热法（ITC）和动态光散射（DLS）的结果表明，EDCs可介导ER二聚化。因此，BRET测定法被证明在检测二聚化并阐明其与EDC诱导的信号传导破坏的相关性方面是有效的。此外，为了检查EDC诱导的转录变化，我们进行了染色质免疫沉淀测序（ChIP-seq），随后进行基因本体（GO）分析。这些分析表明，EDCs影响各种信号通路，包括参与抗体依赖性细胞毒性、心脏诱导中的骨形态发生蛋白（BMP）信号传导以及肝细胞生长因子受体信号传导的通路。总体而言，本研究阐明了EDCs影响ER二聚化和信号传导的分子机制。这些发现突出了基于BRET的测定法在EDC检测中的实用性，并有助于更深入地了解EDCs对内分泌干扰的全身影响。
