Notch 信号通过抑制 ROS 来保护非实质细胞免受体外缺血/再灌注损伤。
Notch signal protects non-parenchymal cells from ischemia/reperfusion injury in vitro by repressing ROS.
机构信息
Department of Hepatic Surgery.
出版信息
Ann Hepatol. 2013 Sep-Oct;12(5):815-21.
BACKGROUND
We have previously reported that Notch signaling pathway protects hepatocytes from ischemia/ reperfusion (I/R) injury by repressing reactive oxygen species (ROS) production. However, apart from hepatocytes, non-parenchymal cells including vascular endothelia cells, Kupffer cells and hepatic stellate cells are also reported to be involved in hepatic I/R injury.
AIM
To clarify the role of Notch signaling in non-parenchymal cells subjected to I/R injury.
MATERIALS AND METHODS
Human Umbilical Vein Endothelial Cells (HUVECs), mouse macrophage line RAW264.7 and rat hepatic stellate cell line HSC-T6 were cultured and subjected to I/R injury, respectively. Activation of Notch signaling was assessed by NICD western blot. Then, pharmacological inhibitor (γ-secretase inhibitor GSI) was used to block Notch signaling of related cell lines in vitro. Intracellular ROS was detected and analyzed by FACS and apoptosis was examined by TUNEL staining and Annexin V staining.
RESULTS
Notch signaling responded to I/R injury and I/R injury induced activation of Notch signaling in nonparenchymal cells. Notch signal deficiency led to overproduction of ROS and aggravated cell death of non-parenchymal cells subjected to I/R injury.
CONCLUSION
Notch signal protects non-parenchymal cells from I/R injury by repressing ROS.
背景
我们之前曾报道过 Notch 信号通路通过抑制活性氧（ROS）的产生来保护肝细胞免受缺血/再灌注（I/R）损伤。然而，除了肝细胞外，非实质细胞如血管内皮细胞、枯否细胞和肝星状细胞也被报道参与肝 I/R 损伤。
目的
阐明 Notch 信号在受 I/R 损伤的非实质细胞中的作用。
材料和方法
培养人脐静脉内皮细胞（HUVECs）、小鼠巨噬细胞系 RAW264.7 和大鼠肝星状细胞系 HSC-T6，并分别进行 I/R 损伤。通过 NICD western blot 评估 Notch 信号的激活。然后，用药理学抑制剂（γ-分泌酶抑制剂 GSI）在体外阻断相关细胞系的 Notch 信号。通过 FACS 检测和分析细胞内 ROS，通过 TUNEL 染色和 Annexin V 染色检测细胞凋亡。
结果
Notch 信号对 I/R 损伤有反应，I/R 损伤诱导非实质细胞中 Notch 信号的激活。Notch 信号缺失导致 ROS 的过度产生，并加重非实质细胞受 I/R 损伤后的细胞死亡。
结论
Notch 信号通过抑制 ROS 来保护非实质细胞免受 I/R 损伤。
Zotero 插件