LTB4-induced inhibition of NOX2 ubiquitination and protease activity is required for NOX2 activation in exocytotic degranulation in human mast cells
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B569
Abstract ID: 4858
Presenting Author:
Myeong Heon Shin , Professor at Yonsei Univ. Col. of Med.
Abstract:
In this study, we investigated whether proteasome-ubiquitin pathway is closely associated with expression of NADPH oxidase 2 (NOX2) and exocytotic degranulation in LTB4-stimulated human mast cells. When HMC-1 cells were simulated with LTB4 for 30 min, amount of NOX2 protein was increased in whole cell lysate compared with results for cells incubated with medium alone. Pretreatment of cells with N-glycosylation inhibitor prevented expression of NOX2, its translocation to the cell surface, ROS generation and exocytotic degranulation induced by LTB4. Moreover, treatment of quiescent cells with an inhibitor of ER mannosidase I or inhibitors of proteasome dramatically induced expression of NOX2 and its translocation to the cell surface. When HMC-1 cells were stimulated with LTB4 for up to 30 min, amounts of ubiquitinated proteins and activity of proteosome were significantly reduced compared with results for cells incubated with medium alone. In IP assay, LTB4 stimulation diminished amount of ubiquitinated NOX2 compared with results for cells stimulated with medium alone. Furthermore, LTB4-induced inhibition of NOX2 ubiquitination and proteosome activity were nicely correlated with translocation of NOX2 to the cell surface and ROS-dependent exocytotic degranulation induced by LTB4. These results suggest that perturbation of NOX2 ubiquitination and proteasome activity play an important role in ROS-mediated exocytotic degranulation in human mast cells induced by LTB4.
LTB4-induced inhibition of NOX2 ubiquitination and protease activity is required for NOX2 activation in exocytotic degranulation in human mast cells
Category
Poster