Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts. | Zhou et al. Arthritis Research Therapy 2011 13 R128 http content 13 4 R128 RESEARCH ARTICLE Open Access Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts 1 1 1 1 2 1 1 Xiaodong Zhou Wei Lin Filemon KTan Shervin Assassi Mavin J Fritzler Xinjian Guo Roozbeh Sharif Tom Xia3 Syeling Lai4 and Frank C Arnett 1 Abstract Introduction Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I topo I which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis SSc exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts a major cell type involved in the fibrotic process. Methods Eleven pairs of fibroblast strains obtained from nonlesional skin biopsies of SSc patients and age sex ethnicity-matched normal controls were examined for catalytic function of nuclear topo I. Immunoprecipitation IP -Western blots were used to examine sumoylation of fibroblast topo I. Real-time quantitative RT-PCR was used to measure transcript levels of SUMO1 and COL1A2 in the fibroblasts. Results Topo I in nuclear extracts of SSc fibroblasts generally showed a significantly lower efficiency than that of normal fibroblasts in relaxing equivalent amounts of supercoiled DNA. Increased sumoylation of topo I was clearly observed in 7 of 11 SSc fibroblast strains. Inhibition of SUMO1 with SUMO1 siRNA improved the catalytic efficiency of topo I in the SSc fibroblasts. In contrast sumoylation of recombinant topo I proteins reduced their catalytic function. Conclusions The catalytic function of topo I was decreased in SSc fibroblasts to which increased sumoylation of topo I may contribute. Introduction Systemic sclerosis SSc is a human multi-system fibrotic disease with high morbidity and mortality but the etiology is largely unknown and
