title: Inhibition of eIF5A results in aberrant uterine natural killer cell function and embryo loss in mice.
abstract: OBJECTIVE
  The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood.
  
  
  METHODS
  The effects of N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A, on the proportion and function of natural killer (NK) cell subsets were investigated using flow cytometry, immunofluorescence, CCK8 assay, TUNEL assay, DNA fragmentation analysis, mitochondrial membrane potential assay, and Western blotting.
  
  
  RESULTS
  Inhibition of eIF5A by GC7 increased embryo loss and reduced the percentage of NK cells in the uterus and spleen. GC7 treatment caused inhibition of NK cell proliferation in a time- and dose-dependent manner. GC7 also induced apoptosis of NK cells. GC7 treatment increased the protein levels of FasL, bax, p53, and cleaved caspase-3. Moreover, GC7 caused loss of mitochondrial membrane potential in NK cells.
  
  
  CONCLUSIONS
  Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Qin
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shi
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Ji
authors.initials: J
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020964:Embryo Loss / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014599:Uterus / Q000187:drug effects / Q000276:immunology*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D051017:Apoptosis Regulatory Proteins; D006147:Guanine; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane
keywords: Abortion; GC7; apoptosis; eIF5A; natural killer cell