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首页> 外文期刊>Chromosome research: An international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology >Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, induces premature separation of sister chromatids during meiosis I and aneuploidy in mouse oocytes in vitro.
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Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, induces premature separation of sister chromatids during meiosis I and aneuploidy in mouse oocytes in vitro.

机译：冈田酸是蛋白磷酸酶1和2A的抑制剂，可在减数分裂I和小鼠卵母细胞非整倍性过程中诱导姐妹染色单体过早分离。

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摘要

Recent advances in understanding some of the molecular aspects of chromosome segregation during mitosis and meiosis provide a background for investigating potential mechanisms of aneuploidy in mammalian germ cells. Numerous protein kinases and phosphatases have important functions during mitosis and meiosis. Alterations in these enzyme activities may upset the normal temporal sequence of biochemical reactions and cellular organelle modifications required for orderly chromosome segregation. Protein phosphatases 1 (PP1) and 2A (PP2A) play integral roles in regulating oocyte maturation (OM) and the metaphase-anaphase transitions. Mouse oocytes were transiently exposed in vitro to different dosages (0, 0.01, 0.1, or 1.0 microg/ml) of the PP1 and PP2A phosphatase inhibitor okadaic acid (OA) during meiosis I and oocytes were cytogenetically analyzed. Significant (p < 0.05) OA dose-response increases in the frequencies of metaphase I (MI) arrested oocytes, MI oocytes with 80 chromatids instead of the normal 20 tetrads, and anaphase I telophase I (AI-TI) oocytes with two groups of an unequal number of chromatids were found. Analysis of MII oocytes revealed significant (p < 0.05) increases in the frequencies of premature sister chromatid separation, single-unpaired chromatids, and hyperploidy. Besides showing that OA is aneugenic, these data suggest that OA-induced protein phosphatase inhibition upsets the normal kinase-phosphatase equilibrium during mouse OM, resulting in precocious removal of cohesion proteins from chromosomes.
机译：在了解有丝分裂和减数分裂过程中染色体分离的某些分子方面的最新进展为研究哺乳动物生殖细胞中非整倍性的潜在机制提供了背景。许多蛋白激酶和磷酸酶在有丝分裂和减数分裂过程中具有重要的功能。这些酶活性的改变可能会扰乱正常的生化反应的时间序列和有序染色体分离所需的细胞器修饰。蛋白磷酸酶1（PP1）和2A（PP2A）在调节卵母细胞成熟（OM）和中期-后期过渡中起着不可或缺的作用。在减数分裂I期间，将小鼠卵母细胞在体外短暂暴露于不同剂量（0、0.01、0.1或1.0 microg / ml）的PP1和PP2A磷酸酶抑制剂冈田酸（OA），并对卵母细胞进行细胞遗传学分析。中期I（MI）停滞的卵母细胞，具有80个染色单体而不是正常20个四联体的MI卵母细胞和具有两组I期末期I末期I（AI-TI）卵母细胞的频率显着（p <0.05）OA剂量反应增加发现不等数量的染色单体。对MII卵母细胞的分析表明，过早的姐妹染色单体分离，单个未配对的染色单体和超倍性的频率显着增加（p <0.05）。除了表明OA具有中性作用外，这些数据还表明OA诱导的蛋白磷酸酶抑制作用会破坏小鼠OM期间正常的激酶磷酸酶平衡，从而导致从染色体上过早地去除凝聚蛋白。

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