Document Detail

The effect of uric acid on homocysteine-induced endothelial dysfunction in bovine aortic endothelial cells.
MedLine Citation:
PMID:  20027155     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Elevated plasma uric acid indicates an increased risk of cardiovascular diseases associated with endothelial dysfunction. However, the role of uric acid in the pathogenesis of endothelial dysfunction is still a matter of debate. It is not clear whether uric acid is a real causative risk factor, an inert marker, or even a protective molecule with respect to its antioxidant properties. We have studied the effect of uric acid on intact endothelial cells as well as cells with homocysteine-induced endothelial dysfunction. DESIGN: Bovine aortic endothelial cells were treated with uric acid (100 - 600 muM) and homocysteine (100 muM) or with uric acid only. After 24 hours, the cells were stimulated with 1 mug/ml of calcium ionophore A23187, and nitric oxide (NO) production was measured electrochemically with the use of a NO-sensitive microelectrode. The expression of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation at Ser1179 was estimated with the use of Western blotting. Interaction between NO and uric acid was measured with a NO electrode. Superoxide generation was measured with the use of the fluorescence dye MitoSox Red. RESULTS: Homocysteine strongly diminished A23187-induced NO release. 100 muM uric acid slightly restored NO production; higher concentrations were ineffective. Interestingly, a dose-dependent decrease of NO release was observed in the cells treated only with uric acid. Uric acid did not scavenge NO and did not change eNOS protein expression or phosphorylation at Ser1179, but dose-dependently increased superoxide production in A23187-stimulated cells. CONCLUSION: In conclusion, uric acid decreased NO bioavailability and enhanced superoxide generation in A23187-stimulated bovine aortic endothelial cells.
Ivana Papezikova; Michaela Pekarova; Antonin Lojek; Lukas Kubala
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuro endocrinology letters     Volume:  30 Suppl 1     ISSN:  0172-780X     ISO Abbreviation:  Neuro Endocrinol. Lett.     Publication Date:  2009  
Date Detail:
Created Date:  2010-02-26     Completed Date:  2010-05-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008373     Medline TA:  Neuro Endocrinol Lett     Country:  Sweden    
Other Details:
Languages:  eng     Pagination:  112-5     Citation Subset:  IM    
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
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MeSH Terms
Blotting, Western
Calcimycin / pharmacology
Cells, Cultured
Endothelial Cells / drug effects,  physiology*
Homocysteine / metabolism,  pharmacology*
Ionophores / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type III / metabolism
Superoxides / metabolism
Time Factors
Uric Acid / metabolism*,  pharmacology*
Reg. No./Substance:
0/Ionophores; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 454-28-4/Homocysteine; 52665-69-7/Calcimycin; 69-93-2/Uric Acid; EC Oxide Synthase Type III

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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