In this study, we report a novel differential nitric oxide interaction with
nonglycosylated and glycosylated hemoglobin. After in vitro incubation of
hemoglobin with S-nitroso N-acetyl penicillamine (SNAP), s-nitrosoglutathio
ne, or S-nitrosocysteine, S-nitrosylation was significantly higher in human
glycosylated hemoglobin purified from diabetic subjects compared to nondia
betic controls. Inversely, spontaneous decomposition was significantly lowe
r for S-nitrosohemoglobin obtained from glycosylated hemoglobin. Bidimensio
nal isoelectric focusing of hemoglobins incubated in vitro with SNAP also r
evealed a greater interaction of nitric oxide with glycosylated hemoglobin.
In addition, a significantly higher level of S-nitrosohemoglobin was found
in erythrocyte lysates from streptozotocin-induced diabetic rats compared
to control Fats. We suggest that highly glycosylated hemoglobin in diabetic
subjects may favor S-nitrosylation, which may in turn impair vascular func
tion, and participate in diabetic microangiopathy. (C) 2000 Academic Press.