腺苷挽救途径和循环AMP调节参与卵母细胞能量代谢。,Scientific Reports

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腺苷挽救途径和循环AMP调节参与卵母细胞能量代谢。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-12-05 , DOI: 10.1038/s41598-019-54693-y
Dulama Richani ₁ , Cathy F Lavea ₁ , Raji Kanakkaparambil _{1,

2} , Angelique H Riepsamen ₁ , Michael J Bertoldo _{1,

3} , Sonia Bustamante ₄ , Robert B Gilchrist ₁

Affiliation

环状AMP（cAMP）中的卵泡峰值及其随后降解为AMP会促进卵母细胞成熟和排卵。体外成熟（IVM）卵母细胞不接受体内发生的cAMP增加，IVM卵丘-卵母细胞复合体中cAMP的人工升高提高了卵母细胞的发展潜力。这项研究检查了小鼠卵母细胞是否可以使用cAMP降解产物AMP通过腺苷挽救途径产生ATP，并研究了IVM卵丘-卵母细胞复合物中cAMP的药理学升高是否改变了ATP水平。用同位素13C5-AMP培养的卵母细胞剂量依赖性地产生13C5-ATP，但是总细胞ATP保持恒定。在IVM之前使用福司柯林和IBMX进行cAMP的药理学升高可降低卵母细胞ATP和ATP：ADP的比例，并促进能量调节剂AMPK的活性。反过来，卵丘细胞表现出较高的ATP，而AMPK没有变化。没有卵母细胞的卵母细胞的培养或它们的间隙连接通讯的抑制产生较低的卵母细胞13C5-ATP，表明卵母细胞通过腺苷挽救途径促进ATP的产生。总之，这项研究表明，小鼠卵母细胞可以通过腺苷挽救途径从AMP产生ATP，而cAMP升高会改变腺苷酸挽救途径的腺嘌呤核苷酸代谢，并可能在精力旺盛的减数分裂成熟过程中通过腺苷挽救途径为AMP提供能量。表明卵丘细胞通过腺苷挽救途径促进了ATP的产生。总之，这项研究表明，小鼠卵母细胞可以通过腺苷挽救途径从AMP产生ATP，而cAMP升高会改变腺苷酸挽救途径的腺嘌呤核苷酸代谢，并可能在精力旺盛的减数分裂成熟过程中通过腺苷挽救途径为AMP提供能量。表明卵丘细胞通过腺苷挽救途径促进了ATP的产生。总之，这项研究表明，小鼠卵母细胞可以通过腺苷挽救途径从AMP产生ATP，而cAMP升高会改变腺苷酸挽救途径的腺嘌呤核苷酸代谢，并可能在精力旺盛的减数分裂成熟过程中通过腺苷挽救途径为AMP提供能量。

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Participation of the adenosine salvage pathway and cyclic AMP modulation in oocyte energy metabolism.

A follicular spike in cyclic AMP (cAMP) and its subsequent degradation to AMP promotes oocyte maturation and ovulation. In vitro matured (IVM) oocytes do not receive the cAMP increase that occurs in vivo, and artificial elevation of cAMP in IVM cumulus-oocyte complexes improves oocyte developmental potential. This study examined whether mouse oocytes can use the cAMP degradation product AMP to generate ATP via the adenosine salvage pathway, and examined whether pharmacological elevation of cAMP in IVM cumulus-oocyte complexes alters ATP levels. Oocytes cultured with isotopic 13C5-AMP dose-dependently produced 13C5-ATP, however total cellular ATP remained constant. Pharmacological elevation of cAMP using forskolin and IBMX prior to IVM decreased oocyte ATP and ATP:ADP ratio, and promoted activity of the energy regulator AMPK. Conversely, cumulus cells exhibited higher ATP and no change in AMPK. Culture of oocytes without their cumulus cells or inhibition of their gap-junctional communication yielded lower oocyte 13C5-ATP, indicating that cumulus cells facilitate ATP production via the adenosine salvage pathway. In conclusion, this study demonstrates that mouse oocytes can generate ATP from AMP via the adenosine salvage pathway, and cAMP elevation alters adenine nucleotide metabolism and may provide AMP for energy production via the adenosine salvage pathway during the energetically demanding process of meiotic maturation.

更新日期：2019-12-05

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