Polycomb group proteins as epigenetic mediators of neuroprotection in ischemic tolerance.
Polycomb group proteins as epigenetic mediators of neuroprotection in ischemic tolerance.
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DOI：
10.1126/scisignal.2000502
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发表时间：
2010-03-02
影响因子：
7.3
通讯作者：
Zhou A
中科院分区：
文献类型：
--
作者：
Stapels M;Piper C;Yang T;Li M;Stowell C;Xiong ZG;Saugstad J;Simon RP;Geromanos S;Langridge J;Lan JQ;Zhou A
将大脑暴露在亚致死性缺血中，会影响对随后的、否则会造成伤害的缺血的反应，导致转录抑制和神经保护，这种反应称为缺血耐受。在这里，我们表明，脑缺血耐受的蛋白质组学特征是转录抑制因子增加，特别是多梳组(PcG)蛋白。在体外模型中，过表达PcG蛋白SCMH1或BMI1可诱导无预适应的缺血耐受。我们发现，PcG蛋白与编码两种钾通道蛋白的基因的启动子区域相关，这两种钾通道蛋白在缺血耐受的大脑中显示丰度降低。此外，PcG蛋白减少了培养的神经细胞的钾电流，并且在没有预适应的情况下击倒钾通道引起了耐受。这些发现揭示了一种以前未知的神经保护机制，涉及PcG家族的基因抑制物。
Exposing the brain to sublethal ischemia affects the response to a subsequent, otherwise injurious ischemia, resulting in transcriptional suppression and neuroprotection, a response called ischemic tolerance. Here, we show that the proteomic signature of the ischemic-tolerant brain is characterized by increased abundance of transcriptional repressors, particularly polycomb group (PcG) proteins. Knocking down PcG proteins precluded the induction of ischemic tolerance, whereas in an in vitro model, overexpressing the PcG proteins SCMH1 or BMI1 induced tolerance to ischemia without preconditioning. We found that PcG proteins are associated with the promoter regions of genes encoding two potassium channel proteins that show decreased abundance in ischemic-tolerant brains. Furthermore, PcG proteins decreased potassium currents in cultured neuronal cells and knocking down potassium channels elicited tolerance without preconditioning. These findings reveal a previously unknown mechanism of neuroprotection that involves gene repressors of the PcG family.