title: Amelioration of compound 4,4'-diphenylmethane-bis(methyl)carbamate on high mobility group box1-mediated inflammation and oxidant stress responses in human umbilical vein endothelial cells via RAGE/ERK1/2/NF-κB pathway.
abstract: High mobility group box-1 (HMGB1), a secreted nuclear protein, acts as an inflammatory mediator and has been implicated in pathophysiological damage of diabetic vascular complications. A compound 4,4'-diphenylmethane-bis(methyl) carbamate (CM1) has a protective activity on advanced glycation end products (AGEs)-induced endothelial dysfunction in our previous study. The aim of this study was to investigate whether CM1 could attenuate HMGB1-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs), and also elucidate the possible underlying mechanism. The pre-treatment of CM1 (10(-9)M) could inhibit significantly the migration of macrophages in co-incubation with HUVECs system. HMGB1 stimulated intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-beta1 (TGF-β1) and receptor for advanced glycation end products (RAGE) protein expression in HUVECs, which were inhibited by pretreatment with CM1. Furthermore, it also reduced significantly reactive oxygen species (ROS) generation and inflammatory cytokine interleukin-6 (IL-6) level in co-incubation system. Immunofluorescence and Western blotting assays showed that CM1 could attenuate HMGB1-induced intracellular ERK1/2 and NF-kB activation in HUVECs. Our findings indicated that CM1 attenuated HMGB1-mediated endothelial activation by ameliorating inflammation and oxidant stress responses via RAGE/ERK1/2/NF-κB pathway.
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, 210028, China. wenmoxiushi@163.com
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Maomao
authors.initials: M
authors.lastname: Zhu
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
authors.forename: Xudong
authors.initials: X
authors.lastname: Cheng
authors.forename: Shumin
authors.initials: S
authors.lastname: Ding
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D002219:Carbamates / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D003920:Diabetes Mellitus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects / Q000473:pathology
chemical_list: C572821:4,4'-diphenylmethane-bis(methyl)carbamate; D002219:Carbamates; D024243:HMGB1 Protein; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D048049:Extracellular Signal-Regulated MAP Kinases