Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity.
Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity.
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S-亚硝基血红蛋白的生化特征。
DOI：
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发表时间：
1999
影响因子：
4.8
通讯作者：
A. Hobbs
中科院分区：
文献类型：
--
作者：
M. Wolzt;R. Macallister;D. Davis;M. Feelisch;S. Moncada;P. Vallance;A. Hobbs
S-亚硝基血红蛋白 (SNO-Hb) 被认为可作为内源性 NO 供体和血压的生理调节剂。然而，SNO-Hb 形成的机制以及 NO 释放和随后的生物活性的机制尚未阐明。在本研究中，已合成并表征了许多亚硝化氧合血红蛋白（HbO(2)）衍生物。 HbO(2) 最多可在三个不同的残基处被亚硝化，一个位于 α 珠蛋白链，两个位于 β 链。由 HbO(2) 和 S-亚硝基谷胱甘肽反应生成的 β 链单亚硝化物质（称为“SNO-Hb”）通过硫醇依赖性机制释放 NO，涉及对 SNO-Hb 亚硝化硫醇官能团的亲核攻击；就谷胱甘肽而言，该过程与混合二硫化物的形成有关。相比之下，多亚硝化血红蛋白种类通过不依赖硫醇的机制释放NO并松弛血管平滑肌。 HbO(2) 可有效清除 SNO-Hb 释放的 NO，并抑制其血管舒张特性。这些数据表明，SNO-Hb 释放的主要血管活性物质是 NO，HNO 是假定的中间体；低分子量硫醇的存在是该过程的先决条件。这些观察结果对 S-亚硝基硫醇的产生、代谢命运和生物活性具有重要意义。
S-Nitrosohemoglobin (SNO-Hb) has been suggested to act as an endogenous NO donor and physiological regulator of blood pressure. However, the mechanisms responsible for the formation of SNO-Hb and those underlying the release of NO and subsequent biological activity have yet to be elucidated. In the present study, a number of nitrosated oxyhemoglobin (HbO(2)) derivatives have been synthesized and characterized. HbO(2) can be nitrosated at up to three distinct residues, one in the alpha-globin chain and two in the beta-chain. A beta-chain mononitrosated species (designated "SNO-Hb"), generated by the reaction of HbO(2) and S-nitrosoglutathione, released NO via a thiol-dependent mechanism involving nucleophilic attack at the nitrosated thiol functionality of SNO-Hb; in the case of glutathione, this process was associated with the formation of a mixed disulfide. In contrast, multinitrosated hemoglobin species released NO and relaxed vascular smooth muscle by a thiol-independent mechanism. HbO(2) scavenged potently NO released from SNO-Hb and inhibited its vasorelaxant properties. These data show that the predominant vasoactive species released from SNO-Hb is NO, with HNO a putative intermediate; the presence of a low molecular weight thiol is a prerequisite for this process. Such observations have important implications for the generation, metabolic fate, and biological activity of S-nitrosothiols.
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DOI：
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发表时间：
1998-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Zhenguo Liu;M. Rudd;Jane E. Freedman;Joseph Loscalzo
通讯作者：
Zhenguo Liu;M. Rudd;Jane E. Freedman;Joseph Loscalzo
影响因子：
3.9
作者：
ISCHIROPOULOS, H;ZHU, L;BECKMAN, JS
通讯作者：
BECKMAN, JS
影响因子：
56.9
作者：
Xu, L;Eu, JP;Stamler, JS
通讯作者：
Stamler, JS
影响因子：
3.9
作者：
BECKMAN, JS;ISCHIROPOULOS, H;TSAI, M
通讯作者：
TSAI, M
DOI：
10.1073/pnas.93.25.14428
发表时间：
1996-12-10
影响因子：
11.1
作者：
Singh, SP;Wishnok, JS;Tannenbaum, SR
通讯作者：
Tannenbaum, SR