Briata P, Bellini C, Vignolo M, Gherzi R
Laboratories of Immunobiology, National Cancer Institute, Genoa, Italy.
Mol Cell Endocrinol. 1991 Jan;75(1):9-14. doi: 10.1016/0303-7207(91)90239-o.
We have studied a 15-year-old girl (P1) suffering from the Hutchinson-Gilford syndrome (progeria) associated with a severe insulin resistance. Insulin binding activity to P1 erythrocytes was 85% reduced when compared to that measured in ten normal controls matched for sex and age. This finding was confirmed in Epstein-Barr virus (EBV)-transformed lymphoblasts and depends on a reduction in insulin receptor number. Also the amount of total insulin receptors, [35S]methionine labeled and immunoprecipitated, was 90% reduced in P1 lymphoblasts when compared to controls. Next, we measured insulin receptor mRNA levels and we found undetectable levels of insulin receptor transcript in P1 EBV-transformed lymphoblasts, in the absence of any rearrangement of insulin receptor gene as evaluated by Southern blot analysis. The marked reduction in insulin receptor gene expression probably accounts for the severe insulin resistance presented by the patient. Despite extensive studies, the molecular basis of progeria is still unknown. The near complete absence of a molecule crucial in the transduction of cell growth and differentiation signals could be involved in the accelerated aging of the patient.
我们研究了一名15岁患有哈钦森-吉尔福德综合征（早老症）并伴有严重胰岛素抵抗的女孩（P1）。与10名年龄和性别匹配的正常对照者相比，P1红细胞的胰岛素结合活性降低了85%。这一发现在用爱泼斯坦-巴尔病毒（EBV）转化的淋巴细胞中得到证实，且这取决于胰岛素受体数量的减少。同样，与对照相比，P1淋巴细胞中经[35S]甲硫氨酸标记并免疫沉淀的总胰岛素受体数量减少了90%。接下来，我们测量了胰岛素受体mRNA水平，发现在P1 EBV转化的淋巴细胞中检测不到胰岛素受体转录本，通过Southern印迹分析评估，胰岛素受体基因没有任何重排。胰岛素受体基因表达的显著降低可能是该患者出现严重胰岛素抵抗的原因。尽管进行了广泛研究，但早老症的分子基础仍然未知。在细胞生长和分化信号转导中起关键作用的分子几乎完全缺失可能与患者的加速衰老有关。
