Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays.

Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays.
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正常和 21 号染色体非整倍体人成纤维细胞中干扰素诱导的多肽的合成:与抗病毒测定中相对敏感性的关系。

DOI:
10.1089/jir.1980.1.111
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发表时间:
1980
期刊:
Journal of interferon research
影响因子:
--
通讯作者:
Epstein,CJ
Epstein,CJ
中科院分区:
--
文献类型:
--
作者:
Weil,J;Epstein,LB;Epstein,CJ

文献摘要

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干扰素物种特异性反应 (IFRC) 基因定位于人类 21 号染色体,激发了人们对 21 号染色体非整倍性对细胞干扰素敏感性影响的兴趣。先前的报告表明,抗病毒测定中测量的 21 三体、二倍体和 21 单体人类成纤维细胞的相对敏感性大于根据 IFRC 基因剂量预测的比率 0.67:1.0:2。作为敏感性的替代测试,我们研究了通过二维凝胶电泳和放射自显影可视化的干扰素诱导的多肽的合成。在鉴定的 10 个此类多肽中,对 2 个二倍体、2 个三体和 1 个单体成纤维细胞菌株中的 3 个进行了定量测量。与抗病毒反应相反,该测试中的相对反应与0.5至5000单位/ml的干扰素浓度范围内的预期基因剂量关系密切对应。这些结果与每个细胞的IFRC基因产物(假定为干扰素受体)的数量与IFRC基因的数量成正比的结论相一致。因此,在抗病毒反应中测量到的非整倍性的放大效应似乎是由干扰素受体合成和干扰素-受体复合物形成之后的某些步骤造成的。
Localization of the gene for the species specific response to interferon(IFRC)to human chromosome 21 has stimulated interest in the effect of aneuploidy for chromosome 21 on cell sensitivity to interferon. Previous reports have shown that the relative sensitivities of trisomy 21, diploid and monosomy 21 human fibroblasts as measured in an antiviral assay are greater than the ratio 0.67: 1.0: 2 predicted on the basis of gene dosage forIFRC. As an alternative test for sensitivity, we have investigated the synthesis of interferon-induced polypeptides visualized by 2-dimensional gel electrophoresis and autoradiography. Of 10 such polypeptides identified, 3 were measured quantitatively in 2 diploid, 2 trisomic, and one monosomic fibroblast strains. In contrast to the antiviral response, the relative responses in this test correspond closely to expected gene dosage relationships over a range of interferon concentrations from 0.5 to 5000 units/ml. These results are compatible with the conclusion that the number ofIFRCgene products (presumed to be the interferon receptor) per cell is proportional to the number ofIFRCgenes. Thus, the amplified effect of aneuploidy as measured in the antiviral response appears to result from some step subsequent to synthesis of interferon receptors and formation of interferon-receptor complexes.