TY - JOUR
T1 - Methylglyoxal and methylglyoxal-arginine adducts do not directly inhibit endothelial nitric oxide synthase
AU - Brouwers, O.
AU - Teerlink, T.
AU - van Bezu, J.
AU - Barto, R.
AU - Stehouwer, C.D.A.
AU - Schalkwijk, C.G.
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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 mu mol/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.
AB - 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 mu mol/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.
U2 - 10.1196/annals.1433.017
DO - 10.1196/annals.1433.017
M3 - Article
C2 - 18079474
SN - 0077-8923
VL - 1126
SP - 231
EP - 234
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -