Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline

• Published in: PloS one 2013-12, Vol.8 (12), p.e82604
• Main Authors: Ma, Xiaotang, Zhang, Huiting, Pan, Qunwen, Zhao, Yuhui, Chen, Ji, Zhao, Bin, Chen, Yanfang
• Format: Article
• Language: English
• Subjects: Age; Animal models; Animals; Biology; Blood-brain barrier; Brain; Breakdown; Breakdowns; Cell Hypoxia; Cell Membrane Permeability - drug effects; Cells, Cultured; Chemistry; Citicoline; Cytidine Diphosphate Choline - pharmacology; Deprivation; Dextran; Dextrans; Dose-Response Relationship, Drug; Down-regulation; Down-Regulation - drug effects; Down-Regulation - genetics; Drug dosages; Endothelial cells; Endothelium; Gene expression; Glucose; Glucose - deficiency; Glucose - pharmacology; Hospitals; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypoxia; Immunofluorescence; Ischemia; Laboratories; Medicine; Mice; Microvasculature; mRNA; Neurology; Oxygen; Oxygen - pharmacology; Permeability; Pharmacology; Proteins; RNA; Rodents; Stroke; Tight Junction Proteins - genetics; Tight Junction Proteins - metabolism; Tight Junctions - drug effects; Tight Junctions - genetics; Tight Junctions - metabolism; Toxicology; Umbilical vein; Zonula occludens-1 protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082604

This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the permeability of HUVECs accompanied with down-regulation of occludens-1 (ZO-1) and occludin at both mRNA and protein levels. Similarly in bEnd.3s, hypoxia increased the permeability and decreased the expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased the permeability in these two models, which paralleled with elevated expression of TJPs. The data demonstrate that citicoline restores the barrier function of endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the expression of TJPs.