FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy.
FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy.
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DOI：
10.1038/srep38090
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发表时间：
2016-11-30
影响因子：
4.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Shen M;Jiang Y;Guan Z;Cao Y;Sun SC;Liu H
氧化应激与卵泡闭锁期间触发颗粒细胞（GC）死亡有关。最近的研究表明，卵泡刺激素（FSH）在保护GC免受氧化损伤方面具有关键作用，尽管确切的机制在很大程度上仍然未知。在这里，我们报告说，FSH促进GC的生存抑制氧化应激诱导的线粒体自噬。FSH处理后，氧化应激引起的GC活力丧失显著降低，这与氧化应激后线粒体自噬活化受损相关。与FSH处理相比，阻断线粒体自噬对氧化应激诱导的GC死亡显示出近似的预防作用，但FSH不能进一步恢复经线粒体自噬抑制剂预处理的细胞的活力。重要的是，FSH抑制氧化应激过程中丝氨酸/苏氨酸激酶PINK 1的诱导。这抑制了E3连接酶帕金的线粒体易位，这是随后清除线粒体所必需的，并最终通过线粒体自噬导致细胞死亡。此外，使用RNAi敲除PINK 1证实了FSH-PINK 1-Parkin-mitophagy途径在氧化条件下调节GC存活的作用。这些发现引入了FSH通过靶向PINK 1-Parkin介导的线粒体自噬保护GC免受氧化损伤的新生理功能。
Oxidative stress has been implicated in triggering granulosa cell (GC) death during follicular atresia. Recent studies suggested that follicle-stimulating hormone (FSH) has a pivotal role in protecting GCs from oxidative injury, although the exact mechanism remains largely unknown. Here, we report that FSH promotes GC survival by inhibiting oxidative stress-induced mitophagy. The loss of GC viability caused by oxidative stress was significantly reduced after FSH treatment, which was correlated with impaired activation of mitophagy upon oxidative stress. Compared with FSH treatment, blocking mitophagy displayed approximate preventive effect on oxidative stress-induced GC death, but FSH did not further restore viability of cells pretreated with mitophagy inhibitor. Importantly, FSH suppressed the induction of serine/threonine kinase PINK1 during oxidative stress. This inhibited the mitochondrial translocation of the E3 ligase Parkin, which is required for the subsequent clearance of mitochondria, and ultimately cell death via mitophagy. In addition, knocking down PINK1 using RNAi confirmed the role of the FSH-PINK1-Parkin-mitophagy pathway in regulating GC survival under oxidative conditions. These findings introduce a novel physiological function of FSH in protecting GCs against oxidative damage by targeting PINK1-Parkin-mediated mitophagy.
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DOI：
10.1186/1477-7827-10-49
发表时间：
2012-06-29
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Agarwal A;Aponte-Mellado A;Premkumar BJ;Shaman A;Gupta S
通讯作者：
Gupta S
DOI：
10.1073/pnas.95.23.13612
发表时间：
1998-11-10
影响因子：
11.1
作者：
Dierich, A;Sairam, MR;Sassone-Corsi, P
通讯作者：
Sassone-Corsi, P
影响因子：
4.8
作者：
Abel, MH;Wootton, AN;Charlton, HM
通讯作者：
Charlton, HM
影响因子：
7.2
作者：
Hulas-Stasiak, Monika;Gawron, Antoni
通讯作者：
Gawron, Antoni
影响因子：
3.9
作者：
Kim, Insil;Rodriguez-Enriquez, Sara;Lemasters, John J.
通讯作者：
Lemasters, John J.