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

[Display omitted] ► Thirty differentially expressed proteins were identified using PF2D in HGPS cells. ► Thirty differentially expressed proteins were grouped into five categories. ► Expression of cytoskeleton proteins were increased in HGPS fibroblasts. ► Elongated G1/G0 with reduced S phase in the cell cycle was identified in HGPS cells. ► Retention of free intracellular Ca2+ concentration was characterized in HGPS cells. 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.