【24h】

Tissue transglutaminase cross-links beclin 1 and regulates autophagy in MPP+-treated human SH-SY5Y cells

机译:组织转谷氨酰胺酶使beclin 1交联并调节MPP +处理的人SH-SY5Y细胞的自噬

获取原文
获取原文并翻译 | 示例
           

摘要

Tissue transglutaminase (tTG) is a cross-linking enzyme involved in protein aggregation during Parkinson's disease (PD) pathogenesis. Autophagy is inhibited by tTG activation via a mechanism in which cross-linking of beclin 1, an autophagy initiator at the level of the endoplasmic reticulum (ER), has been implicated. We reported increased tTG protein levels and activity at the ER in both PD brain and in a PD-mimicking cell system. Here we characterized the interaction between tTG and beclin 1 at the ER membrane and the role of tTG in reduced autophagy in an in vitro model of PD, using differentiated SH-SY5Y neurons treated with the PD-mimic MPP+. We found that under PD-mimicking conditions, beclin 1 and tTG partially colocalized at the ER, beclin 1 levels increased at the ER, and tTG readily cross-linked beclin 1 which was prevented by enzymatic blockade of tTG. Under these conditions, accumulation of beclin 1 at the ER was enhanced by inhibition of tTG activity. In line with these observations and the role of beclin 1 in autophagy, levels of the autophagy marker protein LC3II in MPP+-treated cells, were significantly increased by inhibition of tTG activity. Our data provide first evidence for a role of tTG-mediated regulation of beclin 1 and autophagy in MPP+-treated human SH-SY5Y cells.
机译:组织转谷氨酰胺酶(tTG)是一种在帕金森氏病(PD)发病过程中参与蛋白质聚集的交联酶。自噬被tTG激活通过一种机制抑制,该机制涉及内含网状结构(ER)水平的自噬引发剂beclin 1的交联。我们报道了PD脑和PD模拟细胞系统中ER处tTG蛋白水平和活性的增加。在这里,我们使用PD模拟MPP +处理的分化SH-SY5Y神经元,表征了PD体外模型中tTG和beclin 1在ER膜之间的相互作用以及tTG在减少自噬中的作用。我们发现在模仿PD的条件下,beclin 1和tTG在ER处部分共定位,beclin 1水平在ER处增加,并且tTG易于交联beclin 1,这可通过酶促性阻断tTG来防止。在这些条件下,beclin 1在ER处的积累通过抑制tTG活性而增强。与这些观察结果和beclin 1在自噬中的作用相一致,通过抑制tTG活性显着提高了MPP +处理的细胞中自噬标记蛋白LC3II的水平。我们的数据为tTG介导的Beclin 1调控和自噬在MPP +处理的人SH-SY5Y细胞中的作用提供了第一个证据。

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