title: Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer.
abstract: The macromolecular permeability of cultured bovine aortic, bovine venous, and human umbilical vein endothelial cell monolayers was decreased significantly in culture medium containing L-ascorbic acid (Asc Acid; 0.01-0.1 mM) and L-ascorbic acid 2-phosphate (Asc 2-P). Dithiothreitol, which shows reducing activity equivalent to that of Asc Acid, did not affect endothelial permeability. Asc Acid induced a sixfold increase in collagen synthesis by the endothelial cells. The coexistence of L-azetidine 2-carboxylic acid, an inhibitor of collagen synthesis, attenuated the effect of Asc 2-P in a dose-dependent manner. Another collagen synthesis inhibitor, ethyl-3,4-dihydroxybenzoate, also inhibited collagen synthesis and increased endothelial permeability. The decrease in permeability of the endothelial monolayer was dependent on a reduction of the permeability coefficient of the endothelial monolayer. These findings indicate that endothelial barrier function is stimulated by Asc Acid via an increase in collagen synthesis.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Utoguchi
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Saeki
authors.forename: N
authors.initials: N
authors.lastname: Oka
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D003584:Cytological Techniques; D004229:Dithiothreitol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D013997:Time Factors
chemical_list: D003094:Collagen; D001205:Ascorbic Acid; D004229:Dithiothreitol