Schorderet-Slatkine S, Urner F
Department of Obstetrics and Gynaecology, University of Geneva, Switzerland.
Tokai J Exp Clin Med. 1986 Dec;11(6):453-62.
The pharmacological manipulation of oocyte maturation in vitro offers an interesting tool for the study of the cell division cycle. The molecular mechanisms which are involved in this process are initiated at the oocyte plasma membrane and lead to a cascade of events, such as breakdown of the nuclear membrane (GVBD), chromosome condensation and cell division. Our pharmacological results point to an essential role for membrane in the communication between external information and intracellular signals mediating the physiological process. In Xenopus as well as in mouse oocytes, protein phosphorylation processes appear to be involved, either through the activation/inhibition of protein C kinase (calcium activated and phospholipid-dependent) and/or protein-A-kinase (cAMP dependent). Indeed in both systems, forskolin inhibits the first step of the process (GBVD) assessing the existence of an oocyte adenylate cyclase. Moreover, inhibitors of protein kinase C induce maturation in Xenopus oocyte whereas activators of this kinase prevent the process in denuded mouse oocytes. Interestingly, inhibitors of transmethylation reactions maintain the prophase block in both systems suggesting a role for membrane fluidity (phospholipid methylation) in the regulation of oocyte maturation.
体外对卵母细胞成熟进行药理学调控为细胞分裂周期的研究提供了一个有趣的工具。参与这一过程的分子机制始于卵母细胞的质膜,并引发一系列事件,如核膜破裂(GVBD)、染色体凝聚和细胞分裂。我们的药理学研究结果表明,膜在介导生理过程的外部信息与细胞内信号之间的通讯中起着至关重要的作用。在非洲爪蟾和小鼠卵母细胞中,蛋白质磷酸化过程似乎都参与其中,这可能是通过激活/抑制蛋白C激酶(钙激活且依赖磷脂)和/或蛋白A激酶(cAMP依赖)实现的。实际上,在这两个系统中,福司可林均抑制该过程的第一步(GBVD),这表明卵母细胞腺苷酸环化酶的存在。此外,蛋白激酶C抑制剂可诱导非洲爪蟾卵母细胞成熟,而该激酶的激活剂则可阻止裸鼠卵母细胞的这一过程。有趣的是,转甲基化反应抑制剂在这两个系统中均能维持前期阻滞,这表明膜流动性(磷脂甲基化)在卵母细胞成熟调控中发挥着作用。