由DEHP介导的氧化应激导致莱迪格细胞通过cAMP/PKA/SF-1/StAR通路的丸激素合成受损
Luchen Yang1, Shengzhuo Liu1, Pan Song1
1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China.
Environmental pollution (Barking, Essex : 1987)
|December 10, 2024
概括
通过通过cAMP/PKA/SF-1/StAR通路诱导氧化应激并扰乱合成,暴露于二甲基甲基甲酸盐 (DEHP) 会损害莱迪格细胞 (LCs). 早期识别DEHP作为风险因素对于预防不可逆转的LC损伤至关重要.
科学领域:
- 生殖生物学和毒理学.
- 内分泌学 在内分泌学.
- 毒性的细胞和分子机制.
背景情况:
- 莱迪格细胞 (LC) 损伤可能是不可逆转的,需要早期识别风险因素.
- 疑似造成LC损伤的是常见的环境塑化剂二乙基甲酸盐 (DEHP),这是一种常见的环境塑化剂.
- 对于DEHP影响LC的确切机制尚不清楚.
研究的目的:
- 研究DEHP暴露对莱迪格细胞结构和功能的影响.
- 为了阐明DEHP诱导的莱迪格细胞损伤的潜在分子机制.
- 探索氧化应激和类固醇生成途径在DEHP毒性的作用.
主要方法:
- 使用单细胞RNA测序 (scRNA-seq) 来分析丸细胞群.
- 进行了体外和体内实验,以评估DEHP对LC的影响.
- 利用路径分析 (GO),转录因子活性测定和氧化应激和类固醇生成的生化标志物.
主要成果:
- DEHP破坏了LC的结构和功能,显著改变了类固醇合成和氧化应激通路.
- 暴露于DEHP降低了关键转录因子的活性,特别是类固醇原因子1 (SF-1).
- 通过抑制cAMP/PKA/SF-1/StAR通路,DEHP诱导氧化应激 (增加ROS,降低SOD活性,增加8-OHdG/MDA) 并减少的产生.
结论:
- DEHP主要通过诱导氧化应激来破坏莱迪格细胞功能和类固醇生成.
- 主要的DEHP代谢物MEHP通过损害cAMP/PKA/SF-1/StAR信号级联来抑制的合成.
- 这项研究揭示了对DEHP诱导的莱迪格细胞损伤机制的关键见解,强调DEHP是重要的环境风险因素.
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