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极光激酶A抑制作用会破坏猪胚胎第一次分裂期间的染色体凝聚和纺锤体组装。

Aurora A inhibition disrupts chromosome condensation and spindle assembly during the first embryonic division in pigs.

作者信息

Cui Panpan, Abbasi Benazir, Lin Defeng, Rui Rong, Ju Shiqiang

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

出版信息

Reprod Domest Anim. 2020 May;55(5):584-593. doi: 10.1111/rda.13655. Epub 2020 Feb 29.

Abstract

As common overexpression of Aurora A in various tumours, much attention has focused on its function in inducing cancer, and its value in cancer therapeutics, considerably less is known regarding its role in the first cleavage division of mammalian embryos. Here, we highlight an indispensable role of Aurora A during the first mitotic division progression of pig embryos just after meiosis. The expression and spatiotemporal localization of Aurora A were initially assessed in pig embryos during the first mitotic division by Western blot analysis and indirect immunofluorescent staining. Then, the potential role of Aurora A was further evaluated using a highly selective Aurora A inhibitor, MLN8054, during this mitotic progression in pig embryos. Aurora A was found to express and exhibit a specific dynamic intracellular localization pattern during the first mitotic division in pig embryos. Aurora A was diffused in the cytoplasm at the prophase stage, and then exhibited a dynamic intracellular localization which was tightly associated with the chromosome and spindle dynamics throughout subsequent mitotic phases. Inhibition of Aurora A by MLN8054 treatment led to the failure of the first cleavage, with the majority of embryos being arrested in prophase of the mitotic division. Further subcellular structure examination showed that Aurora A inhibition not only led to the failure of spindle microtubule assembly, but also resulted in severe defects in chromosome condensation, accompanied by an obvious decrease in p-TACC3(S558) expression during the prophase of the first mitosis. Together, these results illustrated that Aurora A is crucial for both spindle assembly and chromosome condensation during the first mitotic division in pig embryos, and that the regulation of Aurora A may be associated with its effects on p-TACC3(S558) expression.

摘要

由于极光激酶A(Aurora A)在各种肿瘤中普遍过表达,其在诱导癌症中的功能及其在癌症治疗中的价值备受关注,而关于其在哺乳动物胚胎第一次卵裂中的作用却知之甚少。在此,我们强调了Aurora A在猪胚胎减数分裂后第一次有丝分裂进程中的不可或缺的作用。通过蛋白质免疫印迹分析和间接免疫荧光染色,最初评估了猪胚胎第一次有丝分裂期间Aurora A的表达和时空定位。然后,在猪胚胎的这个有丝分裂进程中,使用高度选择性的Aurora A抑制剂MLN8054进一步评估了Aurora A的潜在作用。结果发现,Aurora A在猪胚胎第一次有丝分裂期间表达,并呈现出特定的动态细胞内定位模式。在前期阶段,Aurora A在细胞质中呈弥散状态,随后在整个后续有丝分裂阶段呈现出与染色体和纺锤体动态紧密相关的动态细胞内定位。用MLN8054处理抑制Aurora A会导致第一次卵裂失败,大多数胚胎停滞在有丝分裂前期。进一步的亚细胞结构检查表明,抑制Aurora A不仅导致纺锤体微管组装失败,还导致染色体凝聚严重缺陷,同时在第一次有丝分裂前期p-TACC3(S558)表达明显下降。总之,这些结果表明,Aurora A在猪胚胎第一次有丝分裂期间对纺锤体组装和染色体凝聚都至关重要,并且Aurora A的调节可能与其对p-TACC3(S558)表达的影响有关。

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