Cell：卵子为什么随年龄增加而消失的机制被揭示
生物谷报道：我们知道脊椎动物的卵子都会随着年龄增加而逐渐减少，最终消失，从而失去繁殖或生育能力。但为什么会随年龄增长而消失呢？最新一期Cell封面文章揭示了其中的奥秘。Nutt等发现，卵细胞的能量代谢是核心因素，通过能量代谢，从而活化了CaMKII，从而介导caspase-2的活化，导致了卵细胞凋亡。这一研究成果首次将细胞代谢与卵细胞生存联系在一起，这雌性生殖能力的调控提供了新的思路。
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.
原文来源：L.K. Nutt, S.S. Margolis, M. Jensen, C.E. Herman, W.G. Dunphy, J.C. Rathmell, and S. Kornbluth Metabolic Regulation of Oocyte Cell Death through the CaMKII-Mediated Phosphorylation of Caspase-2. Cell, Volume 122, Issue 6. September 23, 2005
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