Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl
Miriam M. Cortese-Krott,Gunter G. C. Kuhnle,Alex Dyson,Bernadette O. Fernandez,Marian Grman,Jenna F. DuMond,Mark P. Barrow,George McLeod,Hidehiko Nakagawa,Karol Ondrias,Péter Nagy,S. Bruce King,Joseph E. Saavedra,Larry K. Keefer,Mervyn Singer,Malte Kelm,Anthony R. Butler,Martin Feelisch +17 more
Reads0
Chats0
TLDR
The 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.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Chemical Biology of H2S Signaling through Persulfidation.
TL;DR: The biologically relevant chemistry of H2S and the enzymatic routes for its production and oxidation are discussed and the roles ascribed to protein persulfidation in cell signaling pathways are discussed.
Journal ArticleDOI
Targeting vascular (endothelial) dysfunction
Andreas Daiber,Sebastian Steven,Alina Weber,Vladimir V. Shuvaev,Vladimir R. Muzykantov,Ismail Laher,Huige Li,Santiago Lamas,Thomas Münzel +8 more
TL;DR: Assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations, and alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio are discussed.
Journal ArticleDOI
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics
Takaaki Akaike,Tomoaki Ida,Fan Yan Wei,Motohiro Nishida,Motohiro Nishida,Yoshito Kumagai,Md. Morshedul Alam,Hideshi Ihara,Tomohiro Sawa,Tetsuro Matsunaga,Shingo Kasamatsu,Akiyuki Nishimura,Masanobu Morita,Kazuhito Tomizawa,Akira Nishimura,Satoshi Watanabe,Kenji Inaba,Hiroshi Shima,Nobuhiro Tanuma,Minkyung Jung,Shigemoto Fujii,Yasuo Watanabe,Masaki Ohmuraya,Péter Nagy,Martin Feelisch,Jon M. Fukuto,Hozumi Motohashi +26 more
TL;DR: Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARS have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo.
Journal ArticleDOI
A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?
Xu Cao,Lei Ding,Zhi-Zhong Xie,Yong Yang,Yong Yang,Matthew Whiteman,Philip K. Moore,Jin-Song Bian +7 more
TL;DR: A bell-shaped model has been proposed to explain the role of H2S in cancer development and indicates that inhibition of H1N1 biosynthesis and H1S supplementation serve as two distinct ways for cancer treatment.
Journal ArticleDOI
A practical guide to working with H2S at the interface of chemistry and biology.
TL;DR: This tutorial review is to provide researchers new to the field of H2S chemical biology with practical considerations, pitfalls, and best practices to enable smooth entry into investigations focused on biological H 2S.
References
More filters
Journal ArticleDOI
Hydrogen sulphide and its therapeutic potential
TL;DR: The physiology and biochemistry of H2S is overviews, the effects of H 2S inhibitors or H2s donors in animal models of disease are summarized, the potential options for the therapeutic exploitation of H1S are outlined and they are outlined.
Journal ArticleDOI
H2S Induces a Suspended AnimationLike State in Mice
TL;DR: It is reported that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species, the house mouse (Mus musculus), and this state is readily reversible and does not appear to harm the animal.
Journal ArticleDOI
Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.
Tomoaki Ida,Tomohiro Sawa,Hideshi Ihara,Yukihiro Tsuchiya,Yasuo Watanabe,Yoshito Kumagai,Makoto Suematsu,Hozumi Motohashi,Shigemoto Fujii,Tetsuro Matsunaga,Masayuki Yamamoto,Katsuhiko Ono,Nelmi O. Devarie-Baez,Ming Xian,Jon M. Fukuto,Takaaki Akaike +15 more
TL;DR: It is proposed that reactive Cys persulfides and S-polythiolation have critical regulatory functions in redox cell signaling and H2S may act primarily as a marker for the biologically active of persulfide species.
Book ChapterDOI
"NONOates" (1-substituted diazen-1-ium-1,2-diolates) as nitric oxide donors: convenient nitric oxide dosage forms
TL;DR: This chapter summarizes relevant physicochemical data, including the NO release rates and product profiles, for a selection of diazeniumdiolate compounds, to help those contemplating new applications of this compound type in research on the pharmacological properties of nitric oxide.
Journal ArticleDOI
Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism
TL;DR: It is shown that precursors of ribonucleotides, amino acids and lipids can all be derived by the reductive homologation of hydrogen cyanide and some of its derivatives, and thus that all the cellular subsystems could have arisen simultaneously through common chemistry.