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

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作者
Ryo Miyamoto
Shin Koike
Yoko Takano
Norihiro Shibuya
Yuka Kimura
Kenjiro Hanaoka
Yasuteru Urano
Yuki Ogasawara
Hideo Kimura
机构
[1] National Institute of Neuroscience,Department of Molecular Pharmacology
[2] National Center of Neurology and Psychiatry,Department of Analytical Biochemistry
[3] Meiji Pharmaceutical University,undefined
[4] Graduate School of Pharmaceutical Sciences,undefined
[5] The University of Tokyo,undefined
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Scientific Reports | / 7卷
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摘要
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.
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