句子翻译：
Oxidative stress-induced granulosa cell (GCs) death represents a common reason for follicular atresia. Follicle-stimulating hormone (FSH) has been shown to prevent GCs from oxidative injury, although the underlying mechanism remains to be elucidated. Here we first report that the suppression of autophagic cell death via some novel signaling effectors is engaged in FSH-mediated GCs protection against oxidative damage. The decline in GCs viability caused by oxidant injury was remarkably reduced following FSH treatment, along with impaired macroautophagic/autophagic flux under conditions of oxidative stress both in vivo and in vitro. Blocking of autophagy displayed similar levels of suppression in oxidant-induced cell death compared with FSH treatment, but FSH did not further improve survival of GCs pretreated with autophagy inhibitors. Further investigations revealed that activation of the phosphoinositide 3-kinase (PI3K)-AKT-MTOR (mechanistic target of rapamycin [serine/threonine kinase]) signaling pathway was required for FSH-mediated GCs survival from oxidative stress-induced autophagy. Additionally, the FSH-PI3K-AKT axis also downregulated the autophagic response by targeting FOXO1, whereas constitutive activation of FOXO1 in GCs not only abolished the protection from FSH, but also emancipated the autophagic process, from the protein level of MAP1LC3B-II to autophagic gene expression. Furthermore, FSH inhibited the production of acetylated FOXO1 and its interaction with Atg proteins, followed by a decreased level of autophagic cell death upon oxidative stress. Taken together, our findings suggest a new mechanism involving FSH-FOXO1 signaling in defense against oxidative damage to GCs by restraining autophagy, which may be a potential avenue for the clinical treatment of anovulatory disorders.
摘要：氧化应激引起的颗粒细胞(GCs)死亡是导致卵泡闭锁的一个常见原因。促卵泡素（FSH）已被证明可以防止GCs受到氧化损伤，但其基本机制仍有待阐明。在此，我们首次报告，通过一些新的信号效应器抑制自噬细胞的死亡，参与了FSH介导的GCs对氧化损伤的保护。在体内和体外的氧化应激条件下，由氧化剂损伤引起的GCs活力下降明显减少，同时宏自噬/自噬通量也受损。与FSH处理相比，阻断自噬对氧化剂诱导的细胞死亡显示出类似的抑制水平，但FSH并没有进一步改善用自噬抑制剂预处理的GCs的生存。进一步的调查显示，磷酸肌肽3-激酶（PI3K）-AKT-MTOR（雷帕霉素[丝氨酸/苏氨酸激酶]的机械性目标）信号通路的激活是FSH介导的GCs从氧化应激诱导的自噬中存活所必需的。此外，FSH-PI3K-AKT轴也通过靶向FOXO1来下调自噬反应，而GCs中FOXO1的构成性激活不仅取消了FSH的保护作用，而且还解放了自噬过程，从MAP1LC3B-II的蛋白水平到自噬基因的表达。此外，FSH抑制了乙酰化FOXO1的产生及其与Atg蛋白的相互作用，随后在氧化压力下自噬细胞的死亡水平下降。综上所述，我们的研究结果表明，FSH-FOXO1信号通过抑制自噬来防御GCs的氧化损伤的新机制，这可能是临床治疗无排卵障碍的一个潜在途径。
期刊Biochemistry, Genetics and Molecular Biology
影响因子：16.016
发表于2017.8.3
词汇整理：