Ascorbate reverses high glucose- and RAGE-induced leak of the endothelial permeability barrier.

Meredith ME, Qu ZC, May JM
Biochem Biophys Res Commun. 2014 445 (1): 30-5

PMID: 24472555 · PMCID: PMC3955275 · DOI:10.1016/j.bbrc.2014.01.078

High glucose concentrations due to diabetes increase leakage of plasma constituents across the endothelial permeability barrier. We sought to determine whether vitamin C, or ascorbic acid (ascorbate), could reverse such high glucose-induced increases in endothelial barrier permeability. Human umbilical vein endothelial cells and two brain endothelial cell lines cultured at 25 mM glucose showed increases in endothelial barrier permeability to radiolabeled inulin compared to cells cultured at 5mM glucose. Acute loading of the cells for 30-60 min with ascorbate before the permeability assay prevented the high glucose-induced increase in permeability and decreased basal permeability at 5mM glucose. High glucose-induced barrier leakage was mediated largely by activation of the receptor for advanced glycation end products (RAGE), since it was prevented by RAGE blockade and mimicked by RAGE ligands. Intracellular ascorbate completely prevented RAGE ligand-induced increases in barrier permeability. The high glucose-induced increase in endothelial barrier permeability was also acutely decreased by several cell-penetrant antioxidants, suggesting that at least part of the ascorbate effect could be due to its ability to act as an antioxidant.

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (23)

Acetylcysteine Animals Antioxidants Ascorbic Acid Benzamides Cell Line Cell Membrane Permeability Cells, Cultured Chromans Cyclic N-Oxides Dithiothreitol Dose-Response Relationship, Drug Endothelial Cells Glucose Glycation End Products, Advanced HMGB1 Protein Humans Human Umbilical Vein Endothelial Cells Mice Receptor for Advanced Glycation End Products Receptors, Immunologic Serum Albumin, Bovine Spin Labels

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