生物
粒体自噬
细胞凋亡
机制(生物学)
SIRT3
细胞生物学
癌症研究
槲皮素
分子生物学
遗传学
生物化学
自噬
基因
物理
量子力学
乙酰化
锡尔图因
抗氧化剂
作者
Shasha Chen,Yidan Wang,Kai Chen,Xinyue Xing,Qihang Jiang,Tong Xu
标识
DOI:10.1016/j.fsi.2024.109907
摘要
Fluorene-9-bisphenol (BHPF), as an alternative to bisphenol A, is now increasingly used in plastic products. The accumulation of BHPF in the water environment has posed potential safety risks to aquatic organisms. Unfortunately, the toxicity of BHPF on the physiological metabolism of aquatic animals remains unclear, especially on the molecular mechanisms of BHPF kidney toxicity and antagonizing BHPF toxicity. Quercetin (QCT), a naturally occurring flavonoid, has been reported to mitigate the toxic effects on aquatic organisms induced by a variety of environmental contaminants. It is unclear whether QCT can be a candidate for mitigating BHPF toxicity. In this study, we investigated the protective effect of QCT on BHPF-induced apoptosis and elucidated the possible mechanism of the protective effect mediated by QCT. We treated epithelioma papulosum cyprini cells (EPCs) with 20 μM of BHPF and/or 20 μM of QCT, and the results showed that BHPF significantly increased the release of reactive oxygen species (ROS) from EPCs, decreased the expression of SIRT3, and initiated endogenous apoptosis. Molecular docking provides evidence for the interaction of QCT and SIRT3. Our intervention with Honokiol (HKL) showed that QCT or HKL treatment significantly attenuated BHPF-induced mitochondrial dysfunction and mitochondrial apoptosis (mtApoptosis) in EPCs, and activated mitophagy, restoring autophagy flux. To further investigate the specific mechanism of the protective effect of QCT, we intervened with Cyclosporin A (CsA), and our results suggest that QCT activation of SIRT3-promoted regulation of mitophagy may be a therapeutic strategy to attenuate the toxic effects of BHPF on EPCs. In conclusion, our findings suggest that BHPF induces oxidative damage and mtApoptosis in EPCs and that QCT activates mitophagy and improves autophagic flux through activation of SIRT3, thereby alleviating apoptosis mediated by mitochondrial dysfunction in EPCs. Our study provides a theoretical basis for reassessing the safety of BHPF for aquatic organisms and reveals a novel detoxification mechanism against the toxic effects of BHPF.
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