Priming of neutrophil oxidative burst in diabetes requires preassembly of the NADPH oxidase

摘要: Hyperglycemia associated with diabetes mellitus results in the priming of neutrophils leading to oxidative stress that is, part, responsible for diabetic complications. p47phox, a NADPH oxidase cytosolic subunit, is key protein assembly superoxide generation. Little known about mechanism pathways people diabetes. In this study, kinetics p47phox activation was investigated by comparing from and healthy subjects, hyperglycemia-induced changes studied using neutrophil-like HL-60 cells as model. resting prematurely translocates cell membrane preassembles p22phox, subunit. This premature translocation preassembly p22phox were also observed cultured high glucose (HG; 25 mM) specific ligand receptor advanced glycation end products (RAGE), S100B. Phosphorylation ERK1/2, but not p38 MAPK, primary signaling pathway, evidenced PD98059 suppressing incubated HG S100B exhibited 1.8-fold increase fMLP-induced generation compared those normal (5.5 mM). These data suggest increased AGE prime inducing stimulating RAGE-ERK1/2 pathway.