在山羊中,APN/AdipoRon通过AMPK/EZH2/H3K27me3调节质类固醇生成
Xiaomeng Pei1, Haolin Li1, Hao Yu1
1College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
The Journal of steroid biochemistry and molecular biology
|December 8, 2024
概括
阿迪波涅丁 (APN) 和阿迪波龙通过破坏AMPK-EZH2相互作用来抑制山羊体黄体 (CL) 类固醇生成,从而导致H3K27me3.3.3的增加. 这种机制影响能量代谢和生殖过程.
科学领域:
- 生殖生物学 生殖生物学
- 细胞的新陈代谢
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- AMP激活蛋白激酶 (AMPK) 对于细胞能量平衡至关重要.
- 亚迪波涅丁 (APN) 和其类似物阿迪波龙 (AdipoRon) 影响质类固醇生成.
- 在APN介导的类固醇生成中AMPK的精确调节作用需要阐明.
研究的目的:
- 调查APN调节山羊体黄体 (CL) 类固醇生成中的AMPK的机制.
- 为了确定山羊CL中AMPK和EZH2之间的相互作用.
- 评估APN/AdipoRon对表观遗传修饰 (H3K27me3,H3K27ac) 和类固醇基因表达的影响.
主要方法:
- 西部斑点 (WB) 和免疫组织化学 (mIHC) 用于分析周期性和孕山羊CL的蛋白质表达和局部化.
- 同免疫沉 (Co-IP) 试验检查了AMPK和EZH2.2之间的相互作用.
- 用APN/AdipoRon,化合物C (AMPK抑制剂) 和GSK126 (EZH2抑制剂) 治疗分离的质细胞,以评估蛋白质表达和表观遗传变化.
主要成果:
- AMPK和EZH2在质细胞的细胞质中同定位和相互作用;H3K27me3和H3K27ac是核的.
- AMPK,EZH2和H3K27ac的表达模式在CL阶段各不相同,在怀孕和周期中期之间具有相似水平,除了EZH2.
- APN/AdipoRon治疗降低了AMPK和H3K27ac,增加了H3K27me3,抑制了类固醇蛋白 (CYP11A1,HSD3B),这被EZH2抑制模仿并被AMPK抑制逆转.
结论:
- 在山羊中,APN/AdipoRon抑制了乳腺类固醇生成.
- 这种抑制通过破坏AMPK-EZH2相互作用而发生,导致H3K27me3.3.增加.
- 这些发现揭示了一种新的表观遗传调节途径,涉及AMPK和EZH2在质功能中.
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