Methylglyoxal causes endothelial dysfunction: the role of endothelial nitric oxide synthase and AMP-activated protein kinase α.
J Basic Clin Physiol Pharmacol
; 25(1): 109-15, 2014 Feb.
Article
in En
| MEDLINE
| ID: mdl-24127540
ABSTRACT
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).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyruvaldehyde
/
Endothelium, Vascular
/
Nitric Oxide Synthase Type III
/
AMP-Activated Protein Kinases
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
J Basic Clin Physiol Pharmacol
Journal subject:
FARMACOLOGIA
/
FISIOLOGIA
Year:
2014
Document type:
Article