Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer.
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.
Utoguchi
N
N
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Ikeda
K
K
Saeki
K
K
Oka
N
N
Mizuguchi
H
H
Kubo
K
K
Nakagawa
S
S
Mayumi
T
T
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
D003094:Collagen; D001205:Ascorbic Acid; D004229:Dithiothreitol