Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, P. R. China.
Biol Reprod. 2020 Aug 21;103(3):534-547. doi: 10.1093/biolre/ioaa081.
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.
研究表明，通过维持高成熟促进因子 (MPF) 活性可以防止排卵后卵母细胞衰老。目前尚不清楚 AMP 激活的蛋白激酶 (AMPK) 是否在排卵后卵母细胞衰老中发挥作用。此外，虽然 AMPK 的激活可刺激小鼠卵母细胞恢复减数分裂，但它会抑制猪和牛卵母细胞的减数分裂恢复。因此，深入研究 AMPK 调节卵母细胞 MPF 活性的种间差异是值得的。本研究表明，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，用化合物 C 失活 AMPK，分别显著增加和减少老化的小鼠卵母细胞的激活易感性 (AS) 和其他老化参数。随着 AMPK 活性的增加，MPF 活性和环腺苷酸 (cAMP) 随排卵后时间的推移显著降低。体外激活和失活 AMPK 分别显著降低和增加 MPF 活性。用 MG132 上调 MPF 或用 roscovitine 下调 MPF 完全消除了 AMPK 激活或失活对老化卵母细胞 AS 的影响。AMPK 通过增加活性氧 (ROS) 和细胞质钙来促进卵母细胞衰老。此外，用 Ca2+/钙调蛋白依赖性蛋白激酶 (CaMK) 抑制剂处理可显著降低 AS 和 AMPK 激活。总之，这些结果表明，AMPK 通过抑制 MPF 活性促进卵母细胞衰老，排卵后卵母细胞衰老通过激活 CaMK 增加 ROS 和细胞质钙，从而降低 cAMP 激活 AMPK。
