Post-ovulatory aging of oocytes disrupts kinase signaling pathways and lysosome biogenesis.
Post-ovulatory aging of oocytes disrupts kinase signaling pathways and lysosome biogenesis.
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DOI：
10.1002/mrd.22413
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发表时间：
2014-10
影响因子：
2.5
通讯作者：
Kinsey, William H.
中科院分区：
文献类型：
--
作者：
McGinnis, Lynda K.;Pelech, Steven;Kinsey, William H.
卵母细胞排卵后的老化导致受精能力和发育能力逐渐丧失。卵母细胞质量的这种下降一直是众多研究的对象，这些研究主要集中在单个信号通路——这对整体信号事件的状态提供的见解有限。本研究的目的是在体外老化过程中全面评估信号通路活性的广泛模式，作为确定可用于防止在长时间培养过程中卵母细胞质量下降的控制点的第一步。对培养8小时前后的卵母细胞进行基于抗体微阵列的磷酸化蛋白质组分析，结果显示在多种蛋白激酶介导的信号通路中发挥作用的43种蛋白质的丰度或激活状态发生了显著变化。通过蛋白质印迹和共聚焦免疫荧光对几个受影响最显著的激酶进行了研究，以证实微阵列的结果。长时间培养导致调节对钙、应激和细胞周期控制的蛋白激酶的丰度和活性发生全局性变化。对细胞内结构的检查显示，大型自噬溶酶体的丰度出现了此前未被认识到的增加，这与蛋白激酶通路的变化相关。这些结果为了解卵母细胞在培养过程中所经历的应激以及由此产生的多种反应提供了依据。观察到的自噬相关活性的增加以及钙信号、细胞周期和应激反应通路的紊乱有可能通过干扰受精后构成卵子激活的正常生化变化顺序而对卵母细胞质量产生负面影响。
Post-ovulatory aging of oocytes results in the progressive loss of fertilization and developmental competence. This degradation of oocyte quality has been the object of numerous investigations, primarily focused on individual signaling pathways – which provide limited insight into the status of global signaling events. The purpose of the present investigation was to comprehensively assess broad patterns of signaling pathway activity during in vitro aging as an initial step in defining control points that can be targeted to prevent the reduction in oocyte quality during prolonged culture. An antibody microarray-based phospho-proteome analysis performed on oocytes before and after eight hours of culture revealed significant changes in the abundance or activation state of 43 proteins that function in a wide variety of protein kinase-mediated signaling pathways. Several of the most significantly affected kinases were studied by Western blot and confocal immunofluorescence to corroborate the array results. Prolonged culture resulted in global changes in the abundance and activity of protein kinases that regulate the response to calcium, stress, and cell-cycle control. Examination of intracellular structures revealed a previously unrecognized increase in the abundance of large autophogagic lysosomes, which correlates with changes in protein kinase pathways. These results provide insight into the stresses experienced by oocytes during culture and the diversity of responses that results from them. The observed increase in autophagy-related activity together with the disruptions in calcium signaling, cell-cycle, and stress-response pathways have the potential to negatively impact oocyte quality by interfering with the normal sequence of biochemical changes that constitute egg activation following fertilization.
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影响因子：
3.7
作者：
Brunet S;Dumont J;Lee KW;Kinoshita K;Hikal P;Gruss OJ;Maro B;Verlhac MH
通讯作者：
Verlhac MH
DOI：
10.1002/mrd.1120240208
发表时间：
1989-10-01
期刊：
GAMETE RESEARCH
影响因子：
--
作者：
BADENAS, J;SANTALO, J;EGOZCUE, J
通讯作者：
EGOZCUE, J
影响因子：
3.8
作者：
Fissore, RA;Kurokawa, M;Smyth, J
通讯作者：
Smyth, J
影响因子：
4.8
作者：
Byron, KL;Lucchesi, PA
通讯作者：
Lucchesi, PA
影响因子：
4.8
作者：
Hoffman, David L.;Brookes, Paul S.
通讯作者：
Brookes, Paul S.