Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels

Ryo Miyamoto,Yoko Takano,Yuka Kimura,Kenjiro Hanaoka,Shin Koike,Yasuteru Urano,Hideo Kimura,Norihiro Shibuya,Yuki Ogasawara

doi:10.1038/srep45995

Abstract

Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca2+ and H2Sn, showed that H2Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH). However, the effects of nitroxyl or nitrosopersulfide, other potential products of H2S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H2Sn are products of synergy between H2S and NO and provides a new insight into the signaling mechanisms.

Highlights

Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature
Two mechanisms of H2S and NO interaction were proposed for angiogenesis: the effect of H2S is mediated by NO through the activation of endothelial NO synthetase in one mechanism[8], while the cooperative action between H2S and NO is essential in another[9]
It is possible that the interaction of H2S with NO produces H2S and NO generates polysulfides (H2Sn)

Summary

Introduction

Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. We show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. The effects of nitroxyl or nitrosopersulfide, other potential products of H2S and NO interaction, are not affected by cyanolysis or reducing substances. Cross talk between H2S and another signaling molecule, nitric oxide (NO), was initially reported as a synergistic effect of relaxation on vascular smooth muscle[2]. Nitroxyl (HNO) generated by the interaction of H2S and NO was proposed to activate transient receptor potential ankyrin 1 (TRPA1) channels[14]. Nitrosopersulfide (SSNO) was reported to be mainly generated from H2S and NO interaction to act as a NO carrier, releasing NO to relax vascular smooth muscles[15]. The application of H2S- or NO-donor alone can produce H2Sn probably due to the interaction with endogenous H2S or NO in mast cells[17]

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Results

Conclusion