...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells
【24h】

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells

机译：食管癌相关基因4是衰老的中枢神经系统前体细胞表达的细胞衰老的分泌诱导物

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mammalian aging is thought to be partially caused by the diminished capacity of stem/precursor cells to undergo self-renewing divisions. Although many cell-cycle regulators are involved in this process, it is unknown to what extent cell senescence, first identified as irreversible growth arrest in vitro, contributes to the aging process. Here, using a serum-induced mouse oligodendrocyte precursor cell (mOPC) senescence model, we identified esophageal cancer-related gene 4 (Ecrg4) as a senescence inducer with implications for the senescence-like state of postmitotic cells in the aging brain. Although mOPCs could proliferate indefinitely when cultured using the appropriate medium (OPC medium), they became senescent in the presence of serum and maintained their senescent phe-notype even when the serum was subsequently replaced by OPC medium. We show that Ecrg4 was up-regulated in the senescent OPCs, its overexpression in OPCs induced senescence by accelerating the proteasome-dependent degradation of cyclins D1 and D3, and that its knockdown by a specific short hairpin RNA prevented these phenotypes. We also show that senescent OPCs secreted Ecrg4 and that recombinant Ecrg4 induced OPC senescence in culture. Moreover, increased Ecrg4 expression was observed in the OPCs and neural precursor cells in the aged mouse brain; this was accompanied by the expression of senescence-associated β-galactosidase activity, indicating the cells' entrance into senescence. These results suggest that Ecrg4 is a factor linking neural-cell senescence and aging.
机译：哺乳动物的衰老被认为部分是由于干细胞/前体细胞自我更新分裂的能力减弱所致。尽管此过程涉及许多细胞周期调节因子，但尚不清楚首先被确定为体外不可逆的生长停滞的细胞衰老在多大程度上促进了衰老过程。在这里，使用血清诱导的小鼠少突胶质细胞前体细胞（mOPC）衰老模型，我们确定了食道癌相关基因4（Ecrg4）作为衰老诱导剂，对衰老脑中有丝分裂后细胞的衰老样状态具有影响。尽管使用适当的培养基（OPC培养基）培养时，mOPC可以无限增殖，但是即使在随后用OPC培养基代替血清的情况下，它们也会在存在血清的情况下衰老并保持其衰老表型。我们显示，Ecrg4在衰老的OPC中被上调，其在OPC中的过表达通过加速细胞周期蛋白D1和D3的蛋白酶体依赖性降解来诱导衰老，并且其被特定的短发夹RNA敲低阻止了这些表型。我们还显示，衰老的OPC分泌Ecrg4，并且重组Ecrg4诱导培养中的OPC衰老。此外，在老年小鼠脑中的OPC和神经前体细胞中观察到Ecrg4表达增加。伴随着衰老相关的β-半乳糖苷酶活性的表达，表明细胞进入了衰老。这些结果表明，Ecrg4是连接神经细胞衰老和衰老的因素。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号