Physiological Ovarian Aging Is Associated with Altered Expression of Post-Translational Modifications in Mice.
Physiological Ovarian Aging Is Associated with Altered Expression of Post-Translational Modifications in Mice.
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小鼠卵巢生理老化与翻译后修饰表达改变有关
DOI：
10.3390/ijms23010002
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发表时间：
2021-12-21
影响因子：
5.6
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Wei M;Li J;Yan H;Luo T;Huang J;Yuan Y;Hu L;Zheng L
翻译后修饰（PTMs）已被证实参与多种女性生殖事件，但其在生理性卵巢衰老中的作用远未阐明。本研究选用3月龄、12月龄和17月龄小鼠（3 M、12 M、17 M）作为生理性卵巢衰老模型。采用实时荧光定量PCR和Western blot方法分别检测小鼠卵巢生理老化过程中雌性生殖功能相关基因的表达、PTM的总体分布、组蛋白修饰和相关调控酶的水平。结果表明，Kbhb的整体蛋白表达（赖氨酸β-羟丁酰赖氨酸），Khib（赖氨酸2-羟基异丁酰赖氨酸），Kglu（赖氨酸戊二酰赖氨酸），Kmal（赖氨酸丙二酰赖氨酸），Ksucc（赖氨酸琥珀酰赖氨酸），Kcr（赖氨酸-巴豆酰赖氨酸），Kbu（赖氨酸丁酰赖氨酸），Kpr（赖氨酸丙酰赖氨酸），SUMO 1随着小鼠年龄的增长，SUMO 1修饰、泛素化、磷酸化和硝基酪氨酸的水平显著增加。此外，Kme 2（赖氨酸二甲基赖氨酸）和Kac（赖氨酸乙酰赖氨酸）的修饰水平在3 M小鼠中最高，在12 M小鼠中最低。此外，只有组蛋白赖氨酸的三甲基化随着年龄的增长而进行性显著上调H4泛素化在12 M和17 M小鼠中明显高于3 M小鼠（p < 0.001（p < 0.001），而Kpr的修改与3 M小鼠中的水平相比，17 M小鼠中的赖氨酸丙酰化（lysine propionylation）和O-GlcNA的水平显著降低（p < 0.05，p < 0.01）。此外，与3 M雌性小鼠相比，编码PTM调节剂的TIP 60、P300、PRDM 9、KMT 5 B和KMT 5C基因的表达水平在17 M雌性小鼠中上调（p < 0.05）。这些结果表明，相关调节酶和PTM的改变与小鼠卵巢生理性衰老有关，有望为延缓卵巢衰老和女性不孕症的诊断与治疗提供有益的见解。
Post-translational modifications (PTMs) have been confirmed to be involved in multiple female reproductive events, but their role in physiological ovarian aging is far from elucidated. In this study, mice aged 3, 12 or 17 months (3M, 12M, 17M) were selected as physiological ovarian aging models. The expression of female reproductive function-related genes, the global profiles of PTMs, and the level of histone modifications and related regulatory enzymes were examined during physiological ovarian aging in the mice by quantitative real-time PCR and western blot, respectively. The results showed that the global protein expression of Kbhb (lysineβ-hydroxybutyryllysine), Khib (lysine 2-hydroxyisobutyryllysine), Kglu (lysineglutaryllysine), Kmal (lysinemalonyllysine), Ksucc (lysinesuccinyllysine), Kcr (lysinecrotonyllysine), Kbu (lysinebutyryllysine), Kpr (lysinepropionyllysine), SUMO1 (SUMO1 modification), ub (ubiquitination), P-Typ (phosphorylation), and 3-nitro-Tyr (nitro-tyrosine) increased significantly as mice aged. Moreover, the modification level of Kme2 (lysinedi-methyllysine) and Kac (lysineacetyllysine) was the highest in the 3M mice and the lowest in 12M mice. In addition, only trimethylation of histone lysine was up-regulated progressively and significantly with increasing age (p < 0.001), H4 ubiquitination was obviously higher in the 12M and 17M mice than 3M (p < 0.001), whereas the modification of Kpr (lysinepropionylation) and O-GlcNA in 17M was significantly decreased compared with the level in 3M mice (p < 0.05, p < 0.01). Furthermore, the expression levels of the TIP60, P300, PRDM9, KMT5B, and KMT5C genes encoding PTM regulators were up-regulated in 17M compared to 3M female mice (p < 0.05). These findings indicate that altered related regulatory enzymes and PTMs are associated with physiological ovarian aging in mice, which is expected to provide useful insights for the delay of ovarian aging and the diagnosis and treatment of female infertility.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Fritz KS;Green MF;Petersen DR;Hirschey MD
通讯作者：
Hirschey MD
DOI：
10.1038/nrm.2016.140
发表时间：
2017-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Sabari BR;Zhang D;Allis CD;Zhao Y
通讯作者：
Zhao Y
影响因子：
7.4
作者：
Garcia-Gimenez，Jose-Luis;Garces，Concepcion;Pallardo，Federico
通讯作者：
Pallardo，Federico
影响因子：
2.9
作者：
Moritz, Benjamin;Woltering, Laura;Goepfert, Ulrich
通讯作者：
Goepfert, Ulrich