亨廷顿病-吉尔福德早衰综合征的蛋白质组学研究：二维色谱法在早老性疾病中的应用。

A proteomic study of Hutchinson-Gilford progeria syndrome: Application of 2D-chromotography in a premature aging disease.

机构信息

Peking University Center of Medical Genetics, Beijing, China.

出版信息

Biochem Biophys Res Commun. 2012 Jan 27;417(4):1119-26. doi: 10.1016/j.bbrc.2011.12.056. Epub 2011 Dec 24.

DOI:10.1016/j.bbrc.2011.12.056

Abstract

The Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease characterized by segmental premature aging. Applying a two-dimensional chromatographic proteomic approach, the 2D Protein Fractionation System (PF2D), we identified 30 differentially expressed proteins in cultured HGPS fibroblasts. We categorized them into five groups: methylation, calcium ion binding, cytoskeleton, duplication, and regulation of apoptosis. Among these 30 proteins, 23 were down-regulated, while seven were up-regulated in HGPS fibroblasts as compared to normal fibroblasts. Three differentially expressed cytoskeleton proteins, vimentin, actin, and tubulin, were validated via Western blotting and characterized by immunostaining that revealed densely thickened bundles and irregular structures. Furthermore in the HGPS cells, the cell cycle G1 phase was elongated and the concentration of free cytosolic calcium was increased, suggesting intracellular retention of calcium. The results that we obtained have implications for understanding the aging process.

摘要

哈钦森-吉尔福德早衰综合征（HGPS）是一种罕见的遗传性疾病，其特征为节段性过早衰老。我们采用二维色谱蛋白质组学方法（2D Protein Fractionation System，PF2D），在培养的 HGPS 成纤维细胞中鉴定出 30 种差异表达蛋白。我们将它们分为 5 组：甲基化、钙离子结合、细胞骨架、复制和细胞凋亡调节。在这 30 种蛋白中，23 种在 HGPS 成纤维细胞中下调，而 7 种在 HGPS 成纤维细胞中上调。通过 Western blot 验证了 3 种差异表达的细胞骨架蛋白，即波形蛋白、肌动蛋白和微管蛋白，并通过免疫染色进行了特征描述，显示出密集增厚的束状结构和不规则结构。此外，在 HGPS 细胞中，细胞周期 G1 期延长，细胞内游离细胞溶质钙离子浓度增加，表明细胞内钙离子滞留。我们的研究结果为理解衰老过程提供了新的认识。