Cell cycle progression and cell division are sensitive to hypoxia in Drosophila melanogaster embryos
Cell cycle progression and cell division are sensitive to hypoxia in Drosophila melanogaster embryos
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DOI：
10.1152/ajpregu.2001.280.5.r1555
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发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
Haddad, GG
中科院分区：
文献类型：
--
作者：
Douglas, RM;Xu, T;Haddad, GG
我们和其他人最近证明，果蝇的黑腹果蝇胚胎停止发育，胚胎细胞在缺乏氧气时停止分裂。为了进一步描述这些胚胎对O-2剥夺的反应，并确定细胞周期中对O-2敏感的检查点，对经历核周期3-13的胚胎进行了O-2剥夺，并在对照、低氧和复氧条件下进行了共聚焦显微镜检查。在体内，对携带绿色荧光蛋白-激动素的胚胎的实时分析表明，细胞在细胞周期的两个主要时间点停滞，要么是在间期(DNA复制之前)，要么是在中期，这取决于诱导O-2剥夺的细胞周期阶段。免疫印迹分析表明，细胞分裂由可诱导串(CDC25同源基因)同步的胚胎在低氧条件下在间期停滞的胚胎中被降解，而在中期停滞的胚胎中不被降解。胚胎在复氧后20min内恢复细胞周期活动，细胞周期动力学变化不明显。我们的结论是，在胚胎细胞周期中，有一些特定的点对黑腹金丝猴的O-2水平敏感。鉴于氧剥夺也会影响其他物种的生长和发育，我们认为在哺乳动物细胞中也可能存在类似的低氧敏感细胞周期检查点。
We and others recently demonstrated that Drosophila melanogaster embryos arrest development and embryonic cells cease dividing when they are deprived of O-2. To further characterize the behavior of these embryos in response to O-2 deprivation and to define the O-2-sensitive checkpoints in the cell cycle, embryos undergoing nuclear cycles 3-13 were subjected to O-2 deprivation and examined by confocal microscopy under control, hypoxic, and reoxygenation conditions. In vivo, real-time analysis of embryos carrying green fluorescent protein-kinesin demonstrated that cells arrest at two major points of the cell cycle, either at the interphase (before DNA duplication) or at metaphase, depending on the cell cycle phase at which O-2 deprivation was induced. Immunoblot analysis of embryos whose cell divisions are synchronized by inducible String (cdc25 homolog) demonstrated that cyclin B was degraded during low O-2 conditions in interphase-arrested embryos but not in those arrested in metaphase. Embryos resumed cell cycle activity within similar to 20 min of reoxygenation, with very little apparent change in cell cycle kinetics. We conclude that there are specific points during the embryonic cell cycle that are sensitive to the O-2 level in D. melanogaster. Given the fact that O-2 deprivation also influences the growth and development of other species, we suggest that similar hypoxia-sensitive cell cycle checkpoints may also exist in mammalian cells.