• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Homocysteine induces human mesangial cell apoptosis via the involvement of autophagy and endoplasmic reticulum stress
【24h】

Homocysteine induces human mesangial cell apoptosis via the involvement of autophagy and endoplasmic reticulum stress

机译：同型半胱氨酸通过自噬和内质网胁迫的参与诱导人体髓细胞凋亡

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

Homocysteine (Hcy) level characterizes a progressive increase in chronic kidney disease (CKD). In fact, Hcy accumulation is considered to be a crucial biochemical culprit in CKD progression, but the mechanism underlying this remains poorly understood. This study investigated the role of Hcy in glomerular mesangial cell (MC) apoptosis and the potential involvement of autophagy and endoplasmic reticulum (ER) stress in this process, shedding light on Hcy toxicity in kidney disease. Human mesangial cells (HMCs) were incubated with different concentrations of Hcy for different times. Flow cytometry was used to determine the proportion of apoptotic cells and western blotting was used to analyze protein levels after the administration of Hcy, endoplasmic reticulum inhibitor 4-phenylbutyric acid (4-PBA), and Atg5 siRNA. The results demonstrated that the cell viability gradually decreased and the proportion of HMCs undergoing apoptosis increased with increasing Hcy concentration and prolonged incubation time. Meanwhile, levels of the apoptosis-related proteins Bax and cleaved caspase-3 were significantly increased, while ER stress-related proteins such as ATF4, CHOP, GRP78, and phospho-eIF2 alpha significantly increased. Levels of cleaved LC3, and beclin1 and Atg5 proteins also increased, accompanied by p62 degradation, indicating autophagy activation. 4-PBA effectively inhibited ER stress and reversed Hcy-induced apoptosis and autophagy. Moreover, Atg5 siRNA alleviated Hcy-induced apoptosis. Taken together, these results suggest that Hcy induces HMC apoptosis in a dose- and time-dependent manner via the activation of Atg5-dependent autophagy triggered by ER stress. This study suggests a novel strategy against Hcy toxicity in kidney injury and should help in clarifying the pathogenesis of CKD.
机译：同型半胱氨酸（Hcy）水平表征慢性肾病（CKD）的渐进增加。事实上，Hcy积累被认为是CKD进展中的一个至关重要的生化罪魁祸首，但是这仍然存在众多的机制仍然清晰。本研究调查了Hcy在肾小球中的作用（MC）凋亡以及自噬和内质网（ER）胁迫的潜在参与在该过程中，在肾脏疾病中脱浊毒性。将人体混蛋细胞（HMC）与不同时间的不同浓度的Hcy一起孵育。流式细胞术用于确定凋亡细胞的比例，用于施用HCY，内质网抑制剂4-苯基丁酸（4-PBA）和ATG5 siRNA后，使用Western印迹分析蛋白质水平。结果表明，细胞活力逐渐降低，HMCs经历细胞凋亡的比例随着Hcy浓度的增加而增加，延长孵育时间。同时，细胞凋亡相关蛋白质Bax和切碎的Caspase-3的水平显着增加，而ER应激相关蛋白如ATF4，CHOP，GRP78和磷酸-EIF2α显着增加。裂解LC3和BEC11和ATG5蛋白的水平也增加，伴随着P62降解，表明自噬激活。 4-PBA有效地抑制ER应激并逆转HCY诱导的细胞凋亡和自噬。此外，ATG5 siRNA缓解了Hcy诱导的细胞凋亡。总之，这些结果表明Hcy通过激活由ER应力触发的ATG5依赖性自噬激活，以剂量和时间依赖性方式诱导HMC凋亡。本研究表明，肾损伤中毒性毒性的新策略，应有助于澄清CKD的发病机制。

著录项

  • 来源
    《RSC Advances》 |2019年第54期|共8页
  • 作者

  • 作者单位
  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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