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Báo cáo y học" Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis. | Fang et al. Respiratory Research 2010 11 61 http respiratory-research.eom content 11 1 61 RESPIRATORY RESEARCH RESEARCH Open Access Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis Danjun Fang21 Richard H West21 Mary E Manson1 Jennifer Ruddy2 Dechen Jiang1 Stephen F Previs3 Nitin D Sonawane1 4 James D Burgess1 and Thomas J Kelley 2 Abstract Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation increased de novo synthesis and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl 6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and AF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell the addition of the CFTR inhibitors Gly H101 or CFTRinh-172 for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h .