期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 34, 页码 E4651-E4660出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1509277112
关键词
sulfide; nitric oxide; nitroxyl; redox; gasotransmitter
资金
- German Research Council [DFG CO 1305/2-1, SFB1116 TP B06]
- European Cooperation in Science and Technology (COST) action [BM1005]
- Slovak Research & Development Agency [APVV-0074-11]
- Marie Curie International Reintegration Grant [PIRG08-GA-2010-277006]
- Hungarian National Science Foundation (OTKA) [K 109843]
- Hungarian Academy of Sciences
- Susanne-Bunnenberg-Stiftung of the Dusseldorf Heart Center
- UK Medical Research Council [G1001536]
- Faculty of Medicine, University of Southampton
- MRC [G1001536] Funding Source: UKRI
- Medical Research Council [G1001536] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [26111012] Funding Source: KAKEN
Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H2S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO-), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO- is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO- synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N2O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H2S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据