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Epimedium promotes steroidogenesis by CREB activation-mediated mitochondrial fusion in endosulfan treated leydig cells
Environmental Toxicology ( IF 4.4 ) Pub Date : 2021-06-05 , DOI: 10.1002/tox.23307
Ho-Lin Chuang, V. Bharath Kumar, Cecilia Hsuan Day, Chih-Chu Ho, Tsung-Jung Ho, Ray-Jade Chen, Viswanadha Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang

Epimedium, is used traditionally in Chinese medicine to treat infertility problems. In this study, we establish the cell model to elucidate the protective effect of epimedium against ES by analyzing the molecular relationship between mitochondrial dynamics and steroidogenesis and to explore the molecular mechanism focusing on mitochondria function relating to fertility. ES induced ROS accumulation in mitochondria and the epimedium treatment significantly reduced the ROS accumulation. Furthermore, mitochondria morphology was restored to elongated shape following epimedium treatment. Epimedium treatment promoted dynamin-associated protein 1 (Drp1)-mediated steroidogenesis pathway by upregulating PKA, CREB, Drp1, and StAR protein expression in response to ES exposure in Leydig cells. Moreover, it was also identified that, CREB plays an important role in epimedium activation in Drp1-mediated steroidogenesis signaling pathway by increasing, phospho-CREB expression in nucleus. Testosterone level is decreased in ES-exposed cells; however, the testosterone level was increased after epimedium treatment. In conclusion, epimedium treatment improved mitochondria function in ES-exposed Leydig cells and activated downstream Drp1-dependent steroidogenesis by CREB mediated signaling pathway.

中文翻译:

淫羊藿通过硫丹处理的睾丸间质细胞中的 CREB ​​活化介导的线粒体融合促进类固醇生成

淫羊藿,传统上用于中医治疗不孕不育问题。在本研究中,我们通过分析线粒体动力学与类固醇生成之间的分子关系,建立细胞模型阐明淫羊藿对ES的保护作用,并探讨线粒体功能与生育力相关的分子机制。ES诱导线粒体中的ROS积累,淫羊藿处理显着降低了ROS积累。此外,在淫羊藿处理后,线粒体形态恢复为细长形状。淫羊藿处理通过上调 PKA、CREB、Drp1 和 StAR 蛋白的表达来促进 dynamin 相关蛋白 1 (Drp1) 介导的类固醇生成途径,以响应 Leydig 细胞中的 ES 暴露。此外,还发现,CREB ​​通过增加细胞核中磷酸化 CREB ​​的表达,在 Drp1 介导的类固醇生成信号通路中的淫羊藿激活中起重要作用。暴露于 ES 的细胞中的睾酮水平降低;然而,淫羊藿治疗后睾酮水平升高。总之,淫羊藿治疗改善了暴露于 ES 的 Leydig 细胞中的线粒体功能,并通过 CREB ​​介导的信号通路激活下游 Drp1 依赖性类固醇生成。
更新日期:2021-08-11
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