title: Effects of calycosin on the impairment of barrier function induced by hypoxia in human umbilical vein endothelial cells.
abstract: The purpose of the present study was to examine the effects of calycosin, an isoflavonoid isolated from Astragali Radix, on the impairment of barrier function induced by hypoxia in cultured human umbilical vein endothelial cells. Hypoxia induced an increase in endothelial cell monolayer permeability, indicating endothelial cell barrier impairment. Endothelial barrier dysfunction induced by hypoxia was accompanied by decreases in cytosolic ATP concentration and cAMP level, the development of actin stress fibers and intercellular gap formation, suggesting that the decreases in cytosolic ATP and cAMP levels and rearrangements of F-actin could be associated with an increase in permeability of endothelial monolayers. Application of calycosin inhibited the hypoxia-induced increase in endothelial permeability in a dose-dependent fashion, which is compatible with inhibition of lactate dehydrogenase release, decrease of the fall in ATP and cAMP contents, and improvement of F-actin rearrangements. These findings indicate that calycosin protected endothelial cells from hypoxia-induced barrier impairment by increasing intracellular energetic sources and promoting regeneration of the cAMP level, as well as improving cytoskeleton remodeling.
authors.affiliation: Institute of Chinese Materia Medica, WHO Collaborating Center for Traditional Medicine, Shanghai University of Traditional Chinese Medicine, 530 LingLing Road, Shanghai 200032, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.forename: Da-Zheng
authors.initials: DZ
authors.lastname: Wu
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Gong
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Zhou
authors.forename: Zhi-Bi
authors.initials: ZB
authors.lastname: Hu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008970:Molecular Weight; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology
chemical_list: D003911:Dextrans; D004365:Drugs, Chinese Herbal; D007529:Isoflavones; C015219:fluorescein isothiocyanate dextran; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D016650:Fluorescein-5-isothiocyanate