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Role of Lipid Raft-ceramide in DUOX1 Activation Induced by TNF-α in Human Bronchial Epithelial

Author: WangLiFen
Tutor: ZhenHongZuo
School: Huazhong University of Science and Technology
Course: Department of Otolaryngology Head and Neck Surgery
Keywords: Lipid rafts Dual oxidase -1 (DUOX1) P47phox Ceramide Tumor necrosis factor -α Airway epithelial cells Methyl-β- cyclodextrin Desipramine
CLC: R562.25
Type: Master's thesis
Year: 2010
Downloads: 26
Quote: 0
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Abstract

Respiratory diseases, such as allergic rhinitis, asthma and other allergic diseases are common. The study found that in its pathogenesis airway hyperresponsiveness is a common pathophysiological features. When airway epithelial cells by in vitro and in vivo inflammation factors stimulate oxidase to produce large amounts of reactive oxygen species by airway epithelial cause airway epithelial damage leading to the occurrence of the disease caused by airway hyperresponsiveness. The dual oxidase -1 (Dual oxidase-1, DUOX1) airway epithelial cells produce reactive oxygen oxidase internal and external stimulation of inflammatory factors, it can catalyze the corresponding substrate to produce superoxide anion and there The role of superoxide dismutase (Superoxide dismutase, SOD) superoxide anion disproportionation of hydrogen peroxide (H ₂ O ₂). Studies have shown that airway epithelial ROS generation plays a major role. Lipid rafts are within the lipid bilayer of cells containing the particular lipid and protein membrane microdomains, which is composed of a large amount of cholesterol and sphingomyelin. When the cells by the stimulation of inflammatory factors, lipid rafts sphingomyelin hydrolysis occurs in the role of the acidic sphingomyelinase, ceramide release large amounts of ceramide, the latter having the nature of spontaneous aggregation, which is capable of cell membrane above small membrane microdomains aggregate to form large platform, oxidase, or the biological activity of macromolecular enzyme complex is formed can be gathered in this platform is activated and the interaction, in order to achieve the transmembrane signal transduction. Signal transduction mechanism of the present study was to investigate the lipid rafts induced tumor necrosis factor α (Tumor necrosis factor-α, TNF-α) DUOX1 enzyme and its regulation in the cytoplasm the subunit P47phox activate and cause airway epithelial damage whether to play a role in the period of allergic rhinitis, chronic bronchitis, asthma and other airway inflammatory disease prevention provide a new strategy. Objective: To investigate lipid rafts - the role of ceramide in TNF-α in the activation the airway epithelium DUOX1 enzyme. Method: 1. Use of sucrose ultracentrifugation isolation lipid rafts and Western blot analysis of lipid rafts extract DUOX1 and P47 ^{phox expression. Using laser confocal observation the cell membrane DUOX1 and P47 ^{phox expression observed both at the same time and the lipid rafts marker protein subunit of cholera toxin B (Cholera toxin B subunit, CTXB) and ceramide (Ceramide) colocalization. 3 reactive oxygen detection kit to detect cell generation of reactive oxygen species. The Results: lipid rafts extract, TNF-α stimulate cell to cause increased DUOX1 and expression in the area of ??lipid rafts P47phox (P lt; 0.05), the lipid rafts interference agents can inhibit TNF-α-induced DUOX1 and P47phox in increased expression (P lt; 0.05); area of ??lipid rafts TNF-α stimulate cell confocal microscopy can be observed in the cell membrane to DUOX1 and P47phox obvious clustering phenomenon occurred, at the same time DUOX1 respectively P47phox, lipid rafts marker cholera toxin and ceramide (Ceramide) showing colocalization phenomenon the, lipid rafts interference agent can inhibit TNF-α-induced DUOX1 and P47phox the cell membrane Shangcu polyethylene as well as co-localization phenomenon; TNF-α stimulation of airway epithelial cells can significantly increases intracellular reactive oxygen species generation (P lt; 0.05), lipid rafts interference agent and DUOX1 The inhibitors can inhibit TNF-α-induced increase in reactive oxygen species (P lt; 0.05). Conclusion: TNF-α can cause airway epithelial cells DUOX1 content of P47phox in lipid rafts increased DUOX1, P47phox transferred to lipid rafts, resulting in the activation of the enzyme, stimulate reactive oxygen increased; acid sphingomyelinase enzyme inhibitor desipramine can suppress the above process, to illustrate the process may depend on the source of ceramide lipid rafts.}}

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CLC: > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Trachea and bronchial disease > Bronchial disease > Bronchial asthma
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