title: 2-amino-phenoxazine-3-one attenuates glucose-induced augmentation of embryonic form of myosin heavy chain, endothelin-1 and plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.
abstract: The aim of this study was to investigate the changes in mRNA level of embryonic form of myosin heavy chain (SMemb), endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1), which are considered to be involved in the angiogenesis and atherosclerosis in diabetic blood vessels, in human umbilical vein endothelial cells (HUVECs) caused by high ambient glucose, and the effects of 2-aminophenoxazine-3-one (Phx-3), which was produced by the reaction of bovine hemoglobin with o-aminophenol, on them. The mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were extensively upregulated in HUVECs treated with high concentration of glucose (15 mM), compared with those in the cells with normal concentration of glucose (5 mM). The migration activity of HUVECs evaluated by the cell migration assay was accelerated by 15 mM glucose. When 10 microM Phx-3, at the concentration of which the proliferation of HUVECs was not affected, was administered to HUVECs with 15 mM glucose, the mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were significantly downregulated to the normal levels in the cells. However, when 10 microM Phx-3 was administered to HUVECs with 5 mM of glucose, the mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were not affected. The migration activity of HUVECs, which was accelerated by high glucose, was reversed by 10 microM Phx-3. The present results suggest that Phx-3 may be a drug to prevent the high glucose-associated endothelial damage, vascular angiogenesis in diabetic patients, by inhibiting the expression of angiogenic factors, such as SMemb, ET-1 and PAI-1, in the endothelial cells.
authors.affiliation: Third Department of Internal Medicine, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Fukuda
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshitake
authors.forename: Zia Ali
authors.initials: ZA
authors.lastname: Khan
authors.forename: Masao
authors.initials: M
authors.lastname: Kanazawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Notoya
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Che
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Akio
authors.initials: A
authors.lastname: Tomoda
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
mesh_terms: D002478:Cells, Cultured; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D010078:Oxazines; D017395:Plasminogen Activator Inhibitor 1; C039203:phenoxazine; D018995:Myosin Heavy Chains; D005947:Glucose