S-NITROSYLATION OF PROTEINS WITH NITRIC-OXIDE - SYNTHESIS AND CHARACTERIZATION OF BIOLOGICALLY-ACTIVE COMPOUNDS
S-NITROSYLATION OF PROTEINS WITH NITRIC-OXIDE - SYNTHESIS AND CHARACTERIZATION OF BIOLOGICALLY-ACTIVE COMPOUNDS
复制标题
DOI：
10.1073/pnas.89.1.444
复制
发表时间：
1992-01-01
影响因子：
11.1
通讯作者：
LOSCALZO, J
中科院分区：
文献类型：
--
作者：
STAMLER, JS;SIMON, DI;LOSCALZO, J
内皮源性舒张因子 (EDRF) 活性归因于高度不稳定的一氧化氮自由基 (NO)。鉴于血浆和细胞环境中含有可快速灭活 NO 的活性物质，推测 NO 通过保持其生物活性的载体分子稳定。还原硫醇物种是这一作用的候选者，在 NO 存在的情况下很容易发生反应，产生比 NO 本身更稳定的具有生物活性的 S-亚硝基硫醇。由于蛋白质中的巯基代表了生物系统中还原硫醇的丰富来源，因此我们研究了几种具有不同性质和功能的含巯基蛋白质在暴露于真正的 NO 和 EDRF 后的反应。我们证明 S-亚硝基蛋白在生理条件下很容易形成，并具有 EDRF 样的血管舒张和血小板抑制作用。这些观察结果表明，蛋白质中的 S-亚硝基硫醇基团可能充当 NO 细胞代谢的中间体，并提出了另一种细胞调节机制的可能性。
Endothelium-derived relaxing factor (EDRF) activity has been attributed to the highly labile nitric oxide radical (NO). In view of the fact that the plasma and cellular milieux contain reactive species that can rapidly inactivate NO, it has been postulated that NO is stabilized by a carrier molecule that preserves its biological activity. Reduced thiol species are candidates for this role, reacting readily in the presence of NO to yield biologically active S-nitrosothiols that are more stable than NO itself. Because sulfhydryl groups in proteins represent an abundant source of reduced thiol in biologic systems, we examined the reaction of several sulfhydryl-containing proteins of diverse nature and function upon exposure to authentic NO and EDRF. We demonstrate that S-nitroso proteins form readily under physiologic conditions and possess EDRF-like effects of vasodilation and platelet inhibition. These observations suggest that S-nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism of NO and raise the possibility of an additional type of cellular regulatory mechanism.