• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides
【24h】

Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides

机译：小GTPase RhoA参与BV2细胞响应原纤维Aβ肽超氧化物生成的调节

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

Fibrillar amyloid-beta (fAβ) peptide causes neuronal cell death, which is known as Alzheimer's disease. One of the mechanisms for neuronal cell death is the activation of microglia which releases toxic compounds like reactive oxygen species (ROS) in response to fAβ. We observed that fAβ rather than soluble form blocked BV2 cell proliferation of microglial cell line BV2, while N-acetyl-l-cysteine (NAC), a scavenger of superoxide, prevented the cells from death, suggesting that cell death is induced by ROS. Indeed, both fAβ_(1-42) and fAβ_(25-35) induced superoxide production in BV2 cells. fAβ_(25-35) produced superoxide, although fAβ_(25-35) is not phagocytosed into BV2 cells. Thus, superoxide production by fAβ does not seem to be dependent on phagocytosis of fAβ. Herein we studied how fAβ produces superoxide in BV2. Transfection of dominant negative (DN) RhoA (N19) cDNA plasmid, small hairpin (sh)-RhoA forming plasmid, and Y27632, an inhibitor of Rho-kinase, abrogated the superoxide formation in BV2 cells stimulated by fAβ. Furthermore, fAβ elevated GTP-RhoA level as well as Rac1 and Cdc42. Tat-C3 toxin, sh-RhoA, and Y27632 inhibited the phosphorylation of p47~(PHOX). Moreover, peritoneal macrophages from p47~(PHOX) (-/-) knockout mouse could not produce superoxide in response to fAβ. These results suggest that RhoA closely engages in the regulation of superoxide production induced by fAβ through phosphorylation of p47~(PHOX) in microglial BV2 cells.
机译：纤维状淀粉样β（fAβ）肽会导致神经元细胞死亡，这被称为阿尔茨海默氏病。神经元细胞死亡的机制之一是小胶质细胞的激活，它响应fAβ释放有毒化合物，例如活性氧（ROS）。我们观察到fAβ而非可溶性形式阻止了小胶质细胞系BV2的BV2细胞增殖，而N-乙酰基-1-半胱氨酸（NAC）（一种超氧化物的清除剂）阻止了细胞的死亡，这表明细胞死亡是由ROS诱导的。实际上，fAβ_（1-42）和fAβ_（25-35）均可诱导BV2细胞中超氧化物的产生。尽管fAβ_（25-35）未被吞噬BV2细胞，但fAβ_（25-35）产生了超氧化物。因此，fAβ产生的超氧化物似乎并不依赖于fAβ的吞噬作用。本文中，我们研究了fAβ如何在BV2中产生超氧化物。显性负（DN）RhoA（N19）cDNA质粒，小发夹（sh）-RhoA形成质粒和Rho激酶抑制剂Y27632的转染消除了fAβ刺激的BV2细胞中超氧化物的形成。此外，fAβ升高了GTP-RhoA水平以及Rac1和Cdc42。 Tat-C3毒素，sh-RhoA和Y27632抑制p47〜（PHOX）的磷酸化。此外，p47〜（PHOX）（-/-）基因敲除小鼠的腹膜巨噬细胞不能响应fAβ产生超氧化物。这些结果表明，RhoA通过小胶质BV2细胞中p47〜（PHOX）的磷酸化密切参与了fAβ诱导的超氧化物的产生。

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