Notch signal protects non-parenchymal cells from ischemia/reperfusion injury in vitro by repressing ROS

Ann Hepatol. Sep-Oct 2013;12(5):815-21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Apoptosis
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Hepatic Stellate Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Macrophages / metabolism
  • Mice
  • Oxidative Stress* / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction* / drug effects

Substances

  • Enzyme Inhibitors
  • Reactive Oxygen Species
  • Receptors, Notch
  • Amyloid Precursor Protein Secretases