赖氨酸琥珀酰化在卵巢衰老中的新兴作用。
The emerging role of lysine succinylation in ovarian aging.
机构信息
School of Public Health and Basic Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Province, Nanchang University, Nanchang, 330006, Jiangxi, China.
出版信息
Reprod Biol Endocrinol. 2023 Apr 20;21(1):38. doi: 10.1186/s12958-023-01088-4.
BACKGROUND
Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc.
METHODS
The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level.
RESULTS
Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc.
CONCLUSION
The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.
背景
卵巢衰老（ovarian aging）是储备功能下降导致卵巢功能障碍甚至降低后代健康质量的过程。然而，卵巢中与衰老相关的分子途径仍不清楚。赖氨酸琥珀酰化（lysine succinylation，Ksuc）是一种新的翻译后修饰（post-translational modification，PTM），在真核生物和原核生物中都广泛保守，并与多种病理生理过程有关。目前尚无相关报道揭示卵巢衰老的分子机制与 Ksuc 之间的联系。
方法
通过免疫印迹和免疫组织化学检测衰老和早发性卵巢功能不全（premature ovarian insufficiency，POI）小鼠卵巢中 Ksuc 的水平。为了进一步探讨 Ksuc 在卵巢衰老中的作用，使用体外小鼠卵巢组织培养和改变 Ksuc 水平的体内小鼠模型。
结果
衰老和 POI 小鼠卵巢中 Ksuc 水平增加，并且 Ksuc 在各种类型的小鼠卵巢细胞中的分布以及在颗粒细胞（granulosa cells，GCs）中的高水平均被揭示。组织学评估和激素水平分析表明，高 Ksuc 水平下调了卵巢指数和抗苗勒管激素（anti-Müllerian hormone，AMH）和雌激素水平，并增加了卵泡闭锁。此外，在高 Ksuc 组中，末端脱氧核苷酸转移酶介导的 dUTP-生物素缺口末端标记（terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling，TUNEL）强度和 Cleaved-caspase-3 的表达增加，B 细胞淋巴瘤-2（B-cell lymphoma-2，Bcl-2）的表达减少，同时与衰老相关的标志物 P21 呈阳性表达。这些结果表明，卵巢衰老可能与 Ksuc 的改变有关。
结论
本研究在小鼠卵巢中鉴定出 Ksuc，并发现高 Ksuc 水平很可能导致卵巢衰老，这有望进一步研究为延缓生理性卵巢衰老和治疗病理性卵巢衰老提供新的信息。
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