Responses of normal and sickle cell hemoglobin to S-nitroscysteine: implications for therapeutic applications of NO in treatment of sickle cell disease

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• 作者：Bonaventura ; Celia ; Godette ; Gerald ; Ferruzzi ; Giulia ; Tesh ; Shirley ; Stevens ; Robert D. ; Henkens ; Robert
• 关键词：Nitrosation ; Sickle cell ; Metal chelator ; SNO-Hb ; Oxidation potential ; Hb ; hemoglobin ; Hb A₀ ; purified hemoglobin of adult human ; SNO-Hb ; S-nitrosylated Hb ; CysNO ; S-nitrosylated cysteine ; EDTA ; ethylenediamine tetraacetic acid ; DPTA ; diethylen
• 刊名：Biophysical Chemistry
• 出版年：2002
• 出版时间：July 10, 2002
• 年：2002
• 卷：98
• 期：1-2
• 页码：165-181
• 全文大小：234 K

文摘

Factors which govern transnitrosation reactions between hemoglobin (Hb) and low molecular weight thiols may define the extent to which S-nitrosated Hb (SNO-Hb) plays a role in NO in the control of blood pressure and other NO-dependent reactions. We show that exposure to S-nitrosylated cysteine (CysNO) produces equivalent levels of SNO-Hb for Hb A₀ and sickle cell Hb (Hb S), although these proteins differ significantly in the electron affinity of their heme groups as measured by their anaerobic redox potentials. Dolphin Hb, a cooperative Hb with a redox potential like that of Hb S, produces less SNO-Hb, indicating that steric considerations outweigh effects of altered electron affinity at the active-site heme groups in control of SNO-Hb formation. Examination of oxygen binding at 5–20 mM heme concentrations revealed increases due to S-nitrosation in the apparent oxygen affinity of both Hb A₀ and Hb S, similar to increases seen at lower heme concentrations. As observed at lower heme levels, deoxygenation is not sufficient to trigger release of NO from SNO-Hb. A sharp increase in apparent oxygen affinity occurs for unmodified Hb S at concentrations above 12.5 mM, its minimum gelling concentration. This affinity increase still occurs in 30 and 60 % S-nitrosated samples, but at higher heme concentration. This oxygen binding behavior is accompanied by decreased gel formation of the deoxygenated protein. S-nitrosation is thus shown to have an effect similar to that reported for other SH-group modifications of Hb S, in which R-state stabilization opposes Hb S aggregation.