title: The role of actin depolymerizing factor in advanced glycation endproducts-induced impairment in mouse brain microvascular endothelial cells.
abstract: Endothelial dysfunction is one of the most important pathological events during the development of several diabetic complications including stroke. The aim of this work was to investigate the role of actin depolymerizing factor (ADF) in advanced glycation endproducts (AGEs)-induced impairment in mouse brain microvascular endothelial cells (MBMECs). Incubation of MBMECs with AGEs led to downregulation of expression of ADF, which was reversed by treatment with soluble receptor of AGEs or tempol (an antioxidant). Incubation of MBMECs with AGEs enhanced ratio of F/G-actin, increased endothelial permeability and reduced vasculogenic property, which was attenuated by overexpression of ADF. Furthermore, overexpression of ADF attenuated AGEs-induced downregulation of zonula occludens-1 and dephosphorylation of vascular endothelial growth factor receptor 2. Incubation of MBMECs with AGEs downregulated dimethylarginine dimethylaminohydrolase 2, enhanced formation of asymmetric dimethylarginine and reduced formation of nitric oxide, which was attenuated by overexpression of ADF. Incubation of MBMECs with AGEs induced activation of NF-κB, upregulated RAGE and enhanced formation of reactive oxygen species, which was attenuated by overexpression of ADF. Additionally, knockdown of ADF aggravated AGEs-induced impairment in endothelial permeability and vasculogenic property in MBMECs. In conclusion, AGEs treatment increased endothelial permeability and reduced vasculogenic property of MBMECs, at least in part, via downregulation of ADF.
authors.affiliation: Department of Neurology, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Rongju
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Di
authors.affiliation: Department of Neurology, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Dengfa
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China. juw301@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D051345:Destrin / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D051345:Destrin; C495825:Dstn protein, mouse; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products
keywords: Actin cytoskeleton; Actin depolymerizing factor; Angiogenesis; Brain; Endothelial permeability