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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board Member: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Haim, Abraham / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu

6 Issues per year

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 25, Issue 1 (Feb 2014)


Methylglyoxal causes endothelial dysfunction: the role of endothelial nitric oxide synthase and AMP-activated protein kinase α

Saadet Turkseven / Elif Ertuna / Gunay Yetik-Anacak / Mukadder Yasa
Published Online: 2013-10-14 | DOI: https://doi.org/10.1515/jbcpp-2013-0095


Background: Methylglyoxal is a major precursor in the formation of advanced glycation end products and is associated with the pathogenesis of diabetes-related vascular complications. The aim of this study was to evaluate whether methylglyoxal induces endothelial dysfunction and to determine the contributors involved in this process.

Methods: Rat thoracic aortic rings were treated for 24 h with 100 μM methylglyoxal by using an organ culture method. A cumulative dose-response curve to acetylcholine was obtained to determine endothelium-dependent relaxation. The protein levels of endothelial nitric oxide synthase (eNOS) and its phosphorylated form at the serine 1177 site [p-eNOS (Ser1177)], heat shock protein 90 (Hsp90), AMP-activated protein kinase α (AMPKα) and its phosphorylated form at the threonine 172 site [p-AMPKα (Thr172)] were evaluated. Superoxide production was determined by lucigenin-chemiluminescence.

Results: Treatment with 100 μM methylglyoxal for 24 h decreased acetylcholine-induced vascular relaxation. The levels of eNOS and p-eNOS (Ser1177) were reduced while no effect on Hsp90 was observed. Levels of p-AMPKα (Thr172) were significantly decreased without any change in total AMPKα protein levels. Superoxide level was not affected by methylglyoxal treatment.

Conclusions: In rat aortic rings, methylglyoxal determines a reduction in endothelium-dependent relaxation. This effect seems to be mediated via a reduction in p-eNOS (Ser1177) and p-AMPKα (Thr172).

Keywords: AMP-activated protein kinase α (AMPKα); endothelium-dependent relaxation; eNOS; methylglyoxal


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About the article

Corresponding author: Saadet Turkseven, Faculty of Pharmacy, Department of Pharmacology, Ege University, 35100 Bornova-Izmir, Turkey, Phone: +90 2323885266, Fax: +90 2323884687, E-mail:

Received: 2013-07-26

Accepted: 2013-09-12

Published Online: 2013-10-14

Published in Print: 2014-02-01

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2013-0095.

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