Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†

Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†
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AMP 激活蛋白激酶在小鼠卵母细胞排卵后衰老过程中的作用 –

DOI:
10.1093/biolre/ioaa081
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发表时间:
2020-05
影响因子:
3.6
通讯作者:
Jing-He Tan
Jing-He Tan
中科院分区:
生物学2区
文献类型:
--
作者:
Guang-Yi Sun;Shuai Gong;Qiao-Qiao Kong;Zhi-Bin Li;Jia Wang;Ming-Tao Xu;Ming-Jiu Luo;Jing-He Tan

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摘要研究表明,维持高促成熟因子(MPF)活性可以防止卵母细胞的老化。AMP激活蛋白激酶(AMPK)是否在排卵后卵母细胞老化中起作用尚不清楚。此外,虽然AMPK的激活刺激小鼠卵母细胞减数分裂的恢复,但它抑制猪和牛卵母细胞减数分裂的恢复。因此,AMPK调节卵母细胞MPF活性的种属差异值得深入研究。该研究表明,用二甲双胍或5-氨基咪唑-4-甲酰胺-1-β-d-呋喃核糖苷激活AMPK和用化合物C灭活AMPK分别显著增加和降低老化小鼠卵母细胞的激活敏感性(AS)和其他老化参数。AMPK活性随排卵时间的延长而升高,MPF活性和环磷酸腺苷(cAMP)则随排卵时间的延长而显著降低。AMPK的激活和失活分别显著降低和增加MPF活性。MG 132上调MPF或roscovitine下调MPF分别完全消除AMPK激活或失活对衰老卵母细胞AS的影响。AMPK促进卵母细胞老化,增加活性氧(ROS)和细胞质钙。此外,治疗与Ca 2 +/钙调素依赖性蛋白激酶(CaMK)抑制剂显着降低AS和AMPK激活。以上结果表明,AMPK通过抑制MPF活性促进卵母细胞老化,而排卵后卵母细胞老化则通过增加ROS和胞浆Ca ~(2+)激活CaMK,从而激活AMPK,降低cAMP水平。AMPK通过抑制MPF活性促进卵母细胞老化,而排卵后卵母细胞老化通过增加ROS和胞浆钙激活CaMK而激活AMPK,同时降低cAMP。
Abstract Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or 5-aminoimidazole-4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cyclic adenosine monophosphate (cAMP) decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium. Summary Sentence AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.
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