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Inhibition of eIF 5A Results in Aberrant Uterine Natural Killer Cell Function and Embryo Loss in Mice
Author(s) -
Qin Xiaoli,
Liu Xiaorui,
Shan Bin,
Shi Lijuan,
Sharma Surendra,
Wu Ji,
Lin Yi
Publication year - 2014
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12194
Subject(s) - flow cytometry , apoptosis , biology , tunel assay , dna fragmentation , microbiology and biotechnology , natural killer cell , chemistry , programmed cell death , cytotoxicity , biochemistry , in vitro
Problem The role of eukaryotic initiation factor 5A ( eIF 5A) in feto‐maternal immunotolerance is poorly understood. Methods of study The effects of N1‐guanyl‐1,7‐diaminoheptane (GC7), an inhibitor of eIF 5A, 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 eIF 5A 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. Conclusion Inhibition of eIF 5A results in aberrant NK cell function and increased embryo loss.