Responses of normal and sickle cell hemoglobin to S-nitroscysteine:: implications for therapeutic applications of NO in treatment of sickle cell disease
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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DOI：
10.1016/s0301-4622(02)00092-3
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发表时间：
2002-07-10
影响因子：
3.8
通讯作者：
Henkens, R
中科院分区：
文献类型：
--
作者：
Bonaventura, C;Godette, G;Henkens, R
控制血红蛋白 (Hb) 和低分子量硫醇之间的转亚硝化反应的因素可以定义 S-亚硝化 Hb (SNO-Hb) 在控制血压和其他 NO 依赖性反应中在 NO 中发挥作用的程度。我们发现，暴露于 S-亚硝基化半胱氨酸 (CysNO) 会产生与 Hb A 和镰状细胞 Hb (Hb S) 相当水平的 SNO-Hb，尽管这些蛋白质在其血红素基团的电子亲和力方面存在显着差异（通过其无氧氧化还原电位测量）。海豚 Hb 是一种具有与 Hb S 类似的氧化还原电位的协同 Hb，产生较少的 SNO-Hb，这表明空间考虑因素超过了活性位点血红素基团电子亲和力改变对 SNO-Hb 形成的影响。对 5-20 mM 血红素浓度下氧结合的检查显示，由于 S-亚硝化，Hb A(0) 和 Hb S 的表观氧亲和力有所增加，与较低血红素浓度下观察到的增加类似。正如在较低血红素水平下观察到的，脱氧不足以触发 SNO-Hb 释放 NO。未修饰的 Hb S 在浓度高于 12.5 mM（其最小胶凝浓度）时，表观氧亲和力急剧增加。这种亲和力增加仍然发生在 30% 和 60% S-亚硝化样品中，但血红素浓度更高。这种氧结合行为伴随着脱氧蛋白质凝胶形成的减少。因此，S-亚硝化具有与报道的 Hb S 的其他 SH 基团修饰类似的效果，其中 R 状态稳定化反对 Hb S 聚集。 (C) 2002 Elsevier Science B.V. 保留所有权利。
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 A, 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 A(0) 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. (C) 2002 Elsevier Science B.V. All rights reserved.