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Biochem Biophys Res Commun. 2014 Feb 28;445(1):30-5. doi: 10.1016/j.bbrc.2014.01.078. Epub 2014 Jan 25.

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

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, United States.
2
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, United States.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, United States; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, United States. Electronic address: james.may@vanderbilt.edu.

Abstract

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.

KEYWORDS:

Ascorbate; Endothelial permeability; High glucose; Oxidative stress; RAGE

PMID:
24472555
PMCID:
PMC3955275
DOI:
10.1016/j.bbrc.2014.01.078
[Indexed for MEDLINE]
Free PMC Article
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