title: Notch signal protects non-parenchymal cells from ischemia/reperfusion injury in vitro by repressing ROS.
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.
  
  
  OBJECTIVE
  To clarify the role of Notch signaling in non-parenchymal cells subjected to I/R injury.
  
  
  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.
  
  
  CONCLUSIONS
  Notch signal protects non-parenchymal cells from I/R injury by repressing ROS.
authors.affiliation: Department of Hepatic Surgery.
authors.forename: Heng-Chao
authors.initials: HC
authors.lastname: Yu
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.forename: Shu-Qiang
authors.initials: SQ
authors.lastname: Yue
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases