Methylglyoxal and methylglyoxal-arginine adducts do not directly inhibit endothelial nitric oxide synthase.
Ann N Y Acad Sci
; 1126: 231-4, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18079474
ABSTRACT
Increased formation of the reactive dicarbonyl compound methylglyoxal (MGO) and MGO-derived advanced glycation end products (AGEs) seems to be implicated in endothelial dysfunction and the development of diabetic vascular complications. MGO reacts with arginine residues in proteins to generate the major glycated adducts 5-hydro-5-methylimidazolone (MG-H1) and argpyrimidine (AP). We investigated whether the free forms of these adducts contribute to vascular cell dysfunction by inhibition of endothelial nitric oxide synthase (eNOS). MG-H1 and AP were synthesized and purified by reversed-phase chromatography, and the conversion of labeled L-arginine to L-citrulline was used to monitor eNOS activity. In contrast to the endogenous eNOS inhibitor asymmetric dimethylarginine (half maximal inhibitory concentration, approximately 5 micromol/L), pathophysiological concentrations of MGO and MG-H1 and AP did not inhibit eNOS activity. Although MGO-derived AGEs are implicated in the development of diabetic vascular complications, this study indicates that this is not mediated via direct inhibition of eNOS activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Aldeído Pirúvico
/
Veias Umbilicais
/
Endotélio Vascular
/
Óxido Nítrico Sintase Tipo III
Limite:
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Holanda