Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2
Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2
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DOI：
10.1016/j.cell.2005.07.032
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发表时间：
2005-10-07
期刊：
影响因子：
64.5
通讯作者：
Kornbluth, S
中科院分区：
文献类型：
--
作者：
Nutt, LK;Margolis, SS;Kornbluth, S
脊椎动物的雌性生殖受到胚胎发育过程中获得的卵母细胞储备的限制。在生物体的一生中，这些细胞会通过细胞凋亡的过程逐渐耗尽。触发这种细胞死亡的计时器尚未确定。我们使用非洲爪哇卵/卵母细胞系统来检验营养储备可以调节卵母细胞活力的假设。我们发现，磷酸戊糖途径产生的NADPH对于卵母细胞的存活是至关重要的，并且这种调节的靶标是caspase-2，以前已经证明，caspase-2是小鼠卵母细胞死亡所必需的。戊糖-磷酸途径通过抑制钙/钙调蛋白依赖的蛋白激酶II(CaMKII)对caspase-2的磷酸化而抑制细胞死亡。这些数据表明，卵母细胞营养耗竭，导致不能产生NADPH，可能是导致卵子细胞凋亡的原因之一。这些数据还提供了卵母细胞代谢、CaMKII和caspase-2之间意想不到的联系。
Vertebrate female reproduction is limited by the oocyte stockpiles acquired during embryonic development. These are gradually depleted over the organism's lifetime through the process of apoptosis. The timer that triggers this cell death is yet to be identified. We used the Xenopus egg/oocyte system to examine the hypothesis that nutrient stores can regulate oocyte viability. We show that pentose-phosphate-pathway generation of NADPH is critical for oocyte survival and that the target of this regulation is caspase-2, previously shown to be required for oocyte death in mice. Pentose-phosphate-pathway-mediated inhibition of cell death was due to the inhibitory phosphorylation of caspase-2 by calcium/calmodulin-dependent protein kinase II (CaMKII). These data suggest that exhaustion of oocyte nutrients, resulting in an inability to generate NADPH, may contribute to ooctye apoptosis. These data also provide unexpected links between oocyte metabolism, CaMKII, and caspase-2.