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Hyperglycaemia promotes cerebral barrier dysfunction through activation of protein kinase C-β

Shao, B.; Bayraktutan, U.

Authors

B. Shao



Abstract

Aim: To examine whether protein kinase C (PKC) and associated downstream mechanisms are involved in hyperglycaemia (HG)-evoked blood-brain barrier (BBB) damage. Methods: The activities of total PKC (Peptag assay), NADPH oxidase (lucigenin assay) and matrix metalloproteinase-2 (MMP-2; gelatin zymography) were measured in human brain microvascular endothelial cells (HBMEC) exposed to normoglycaemia (5.5mM) or HG (25mM) using the specific assays indicated in parentheses. The integrity and function of the in vitro models of human BBB were assessed by measurements of transendothelial electrical resistance and paracellular flux of permeability markers, respectively. Occludin protein expression was studied by immunoblotting. Results: HG significantly compromised the BBB integrity and enhanced total PKC activity to which increases in PKC-β and PKC-βII isoforms contributed the most. Elevations in NADPH oxidase and MMP-2 activities and decreases in occludin levels contributed to barrier dysfunction. Selective inhibition of PKC-β isoform prevented the changes observed in occludin expression and the aforementioned enzyme activities and thus effectively preserved barrier integrity. Similarly, apocynin, a specific NADPH oxidase inhibitor, also effectively neutralized the effects of HG on barrier integrity, MMP-2 activity, occludin expression and PKC-β activity. Conclusion: HG promotes cerebral-barrier dysfunction through activation of PKC-β and consequent stimulations of oxidative stress and tight junction dissolution. © 2013 John Wiley & Sons Ltd.

Journal Article Type Article
Publication Date Apr 25, 2013
Journal Diabetes, Obesity and Metabolism
Print ISSN 1462-8902
Electronic ISSN 1463-1326
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 15
Issue 11
Pages 993-999
APA6 Citation Shao, B., & Bayraktutan, U. (2013). Hyperglycaemia promotes cerebral barrier dysfunction through activation of protein kinase C-β. Diabetes, Obesity and Metabolism, 15(11), 993-999. https://doi.org/10.1111/dom.12120
DOI https://doi.org/10.1111/dom.12120
Keywords Internal Medicine; Endocrinology, Diabetes and Metabolism; Endocrinology
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