Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.
Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.
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泛素样修饰剂 1 连接酶 1 通过减少颗粒细胞内质网应激缓解顺铂诱导的卵巢早衰
DOI：
10.1186/s12958-022-00956-9
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发表时间：
2022-05-24
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影响因子：
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泛素样修饰物1连接酶1 （UFL1）是UFMylation系统的连接酶，最近被报道参与多种疾病的细胞凋亡和内质网应激（ER应激）。卵巢早衰（POF）是一种严重降低女性生育能力的妇科疾病，尤其是在接受化疗药物的女性癌症患者中。UFL1是否参与对化疗诱导的POF的保护及其机制尚不清楚。本研究通过组织学检查和细胞活力分析，探讨了UFL1在顺铂诱导的卵巢功能障碍和颗粒细胞（GC）凋亡中的作用。采用western blotting、qPCR和免疫荧光（IF）检测UFL1的表达和内质网应激特异性标志物的水平。采用酶联免疫吸附法检测卵巢和GCs中促卵泡激素（FSH）和雌激素（E2）水平。此外，我们使用慢病毒颗粒悬浮液感染，分别在卵巢和GCs中敲低和过表达UFL1。我们的数据显示，POF模型卵巢中UFL1的表达降低，并伴有内质网应激。在体外，顺铂诱导GCs中与应激相关的UFL1表达升高，并增强内质网应激，UFL1敲低加重内质网应激，UFL1过表达减轻内质网应激。此外，UFL1敲低导致卵巢卵泡数量减少，闭锁卵泡增加，AMH和FSHR表达降低。相反，在体外，UFL1的过表达减少了顺铂诱导的卵巢损伤。我们的研究表明，UFL1调节顺铂诱导的GCs内质网应激和凋亡，参与顺铂诱导的POF的保护，为临床预防化疗药物性POF提供了潜在的治疗靶点。在线版本包含补充材料，可在10.1186/s12958-022-00956-9获得。
Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1), the ligase of the UFMylation system, has recently been reported to be involved in apoptosis and endoplasmic reticulum stress (ER stress) in a variety of diseases. Premature ovarian failure (POF) is a gynecological disease that severely reduces the fertility of women, especially in female cancer patients receiving chemotherapy drugs. Whether UFL1 is involved in protection against chemotherapy-induced POF and its mechanism remain unclear. In this study, we examined the function of UFL1 in ovarian dysfunction and granulosa cell (GC) apoptosis induced by cisplatin through histological examination and cell viability analysis. We used western blotting, quantitative real-time PCR (qPCR) and immunofluorescence (IF) to detect the expression of UFL1 and the levels of ER stress specific markers. Enzyme linked immunosorbent assays were used to detect the levels of follicle-stimulating hormone (FSH) and estrogen (E2) in ovaries and GCs. In addition, we used infection with lentiviral particle suspensions to knock down and overexpress UFL1 in ovaries and GCs, respectively. Our data showed that the expression of UFL1 was reduced in POF model ovaries, accompanied by ER stress. In vitro, cisplatin induced a stress-related increase in UFL1 expression in GCs and enhanced ER stress, which was aggravated by UFL1 knockdown and alleviated by UFL1 overexpression. Furthermore, UFL1 knockdown resulted in a decrease in ovarian follicle number, an increase in atretic follicles, and decreased expression of AMH and FSHR. Conversely, the overexpression of UFL1 reduced cisplatin-induced damage to the ovary in vitro. Our research indicated that UFL1 regulates cisplatin-induced ER stress and apoptosis in GCs, and participates in protection against cisplatin-induced POF, providing a potential therapeutic target for the clinical prevention of chemotherapeutic drug-induced POF. The online version contains supplementary material available at 10.1186/s12958-022-00956-9.
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DOI：
10.6118/jmm.2018.24.3.196
发表时间：
2018-12-01
期刊：
Journal of menopausal medicine
影响因子：
--
作者：
Lee, Eun Hee;Han, Si Eun;Lee, Kyu Sup
通讯作者：
Lee, Kyu Sup
影响因子：
1.9
作者：
Buratini, J., Jr.;Price, C. A.
通讯作者：
Price, C. A.
影响因子：
64.8
作者：
Johnson, J;Canning, J;Tilly, JL
通讯作者：
Tilly, JL
影响因子：
11.4
作者：
Komatsu, M;Chiba, T;Tanaka, K
通讯作者：
Tanaka, K
FSH通过抑制自噬对抗小鼠卵巢颗粒细胞氧化损伤的保护机制
影响因子：
13.3
作者：
Shen, Ming;Jiang, Yi;Sun, Shao-chen
通讯作者：
Sun, Shao-chen