title: Enhancement of S-nitrosylation in glycosylated hemoglobin.
abstract: 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-nitrosoglutathione, or S-nitrosocysteine, S-nitrosylation was significantly higher in human glycosylated hemoglobin purified from diabetic subjects compared to nondiabetic controls. Inversely, spontaneous decomposition was significantly lower for S-nitrosohemoglobin obtained from glycosylated hemoglobin. Bidimensional isoelectric focusing of hemoglobins incubated in vitro with SNAP also revealed 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 rats. We suggest that highly glycosylated hemoglobin in diabetic subjects may favor S-nitrosylation, which may in turn impair vascular function, and participate in diabetic microangiopathy.
authors.affiliation: Deparatamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Padrón
authors.forename: C
authors.initials: C
authors.lastname: Peiró
authors.forename: E
authors.initials: E
authors.lastname: Cercas
authors.forename: J L
authors.initials: JL
authors.lastname: Llergo
authors.forename: C F
authors.initials: CF
authors.lastname: Sánchez-Ferrer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000737:chemistry* / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D013997:Time Factors
chemical_list: D003545:Cysteine; D006442:Glycated Hemoglobin; D006454:Hemoglobins; D009569:Nitric Oxide; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; C021315:S-nitrosocysteine