由于影响Plod1相关的原蛋白形成,SIRT6缺乏会导致卵巢低成形
Liyuan Li1,2, Rui Hua1, Kaiqiang Hu1
1Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, PR China.
Aging cell
|November 8, 2023
概括
缺少SIRT6会破坏卵巢发育和卵泡生长,因为会损害原蛋白的形成和雌激素的生物合成. 这突出了SIRT6的功能.
科学领域:
- 分子生物学分子生物学
- 生殖生物学 生殖生物学
- 老年学是一门学科.
背景情况:
- 赛尔图因6 (SIRT6) 是一种依赖NAD+的脱乙酶,参与新陈代谢,DNA修复和衰老.
- 卵巢衰老涉及卵泡数量和卵细胞质量的减少,SIRT6表达的减少与卵巢储备的减少有关.
- 在卵巢卵泡发育中SIRT6的确切作用仍然在很大程度上未被描述.
研究的目的:
- 研究SIRT6在卵巢卵泡发育中的功能.
- 阐明SIRT6在卵巢衰老和功能中的作用背后的分子机制.
主要方法:
- 使用了SIRT6淘汰赛 (KO) 小鼠和SIRT6淘汰赛 (KD) 在颗粒细胞 (GC) 中.
- 评估卵巢发育,青春期,雌性周期,卵泡数量,原水平和基因/蛋白质表达.
- 分析了雌激素生物合成和炎症途径标记物 (TNF-α,NF-κB).
主要成果:
- 缺少SIRT6会中断卵巢发育,导致青春期和雌性周期的中断.
- SIRT6 KO小鼠表现出二次性和毛囊的减少以及卵巢 stromal 原蛋白的减少.
- 在SIRT6缺乏的卵巢和GC中观察到PLOD1降低,异常的雌激素水平和雌激素合成基因 (CYP11A1,CYP19A1,MGARP) 的改变表达.
- 在SIRT6缺陷模型中发现了TNF-α和NF-κB水平的增加.
结论:
- SIRT6在哺乳动物的卵巢卵泡发育中起着至关重要的作用.
- 通过调节雌激素生物合成和原形成,SIRT6会影响卵巢功能.
- 对于与年龄相关的卵巢功能障碍,SIRT6可能成为潜在的治疗标.
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