Inhibition of eIF5A results in aberrant uterine natural killer cell function and embryo loss in mice.

Inhibition of eIF5A results in aberrant uterine natural killer cell function and embryo loss in mice.
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抑制 eIF5A 导致小鼠子宫自然杀伤细胞功能异常和胚胎丢失

DOI:
10.1111/aji.12194
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发表时间:
2014-03
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
--
通讯作者:
Lin Y
Lin Y
中科院分区:
其他
文献类型:
--
作者:
Qin X;Liu X;Shan B;Shi L;Sharma S;Wu J;Lin Y

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真核起始因子5A (eIF5A)在胎母免疫耐受中的作用尚不清楚。采用流式细胞术、免疫荧光、CCK8、TUNEL、DNA片段化、线粒体膜电位、western blotting等方法研究eIF5A抑制剂n1 -鸟酰-1,7-二氨基庚烷(GC7)对自然杀伤细胞(NK)亚群比例和功能的影响。GC7对eIF5A的抑制增加了胚胎丢失,降低了子宫和脾脏中NK细胞的百分比。GC7对NK细胞增殖的抑制呈时间和剂量依赖性。GC7还能诱导NK细胞凋亡。GC7处理增加了FasL、bax、p53和cleaved caspase 3的蛋白水平。GC7引起NK细胞线粒体膜电位丧失。抑制eIF5A导致NK细胞功能异常和胚胎丢失增加。
The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood. 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. 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. Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.
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