WU Li-Li, WANG Li-Qun, WANG Da, and HUANG Qiao-Bing
(Department of Pathophysiology, Southern Medical University, The Key Laboratory of Shock and Microcirculation of Guangdong Province, Guangzhou, Guangdong 510515, China) 在知网中查找 在百度中查找 在本站中查找
Aim To demonstrate the activation and nuclear translocation of the nuclear factor-κB(NF-κB) induced by advanced glycation end products (AGEs) in human dermal microvascular endothelial cells (HDMECs) , and to elucidate the roles of oxidative stress and endoplasmic reticulum stress in this pathological procedure. Methods HDMECs were incubated with AGEs-modified bovine serum albumin (AGE-BSA) at concentration of 100 mg/L for 1 h. As control, BSA of the same concentration was administered to HDMECs. NF-κB nuclear translocation was observed by immunofluorescent staining. Subsequently, HDMECs were pretreated with reduced glutathione (GSH), apocynin, a pharmacological inhibitor of NADPH oxidase (NOX), NOX4 siRNA or inositol requiring enzyme 1α (IRE1α) siRNA, and then administrated with AGE-BSA for 1 h. Changes of NF-κB nuclear translocation was observed. Results The results demonstrated the translocation of NF-κB from the cytoplasm to the nucleus upon the stimulation of AGE-BSA. Inhibition of reactive oxygen species generation with GSH or apocynin greatly attenuated these responses. Transfection of NOX4-small interfering RNA or IRE1α-small interfering RNA in HDMECs also significantly attenuated the AGE-induced translocation of NF-κB. Conclusion Oxidative stress and endoplasmic reticulum stress are possibly involved in the mediation of AGE-induced activation of NF-κB in endothelial cells.