Polysulfide activates TRP channels and increases intracellular Ca2+ in astrocytes

Oosumi, Kimiko; Tsugane, Mamiko; Ishigami, Mari; Nagai, Yasuo; Iwai, Takashi; Oka, Jun-Ichiro; Kimura, Hideo

doi:10.1016/j.neures.2010.07.2052

Cited by 26 publications

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“…The oxidation of H 2 S generates H 2 S n 2021222329, and the interaction of H 2 S with S-nitroso cysteine generates cysteine persulfide3031. Therefore, it is possible that the interaction of H 2 S with NO produces H 2 S n .…”

Section: Resultsmentioning

confidence: 99%

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

Miyamoto

Koike

Takano

et al. 2017

Sci Rep

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114

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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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Section: Resultsmentioning

confidence: 99%

“…In addition, H 2 S n activate TRPA1 channels by sulfurating two cysteine residues at the amino-termini of the channels21222324. Various other effects of H 2 S n were subsequently reported.…”

mentioning

confidence: 99%

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

Miyamoto

Koike

Takano

et al. 2017

Sci Rep

Self Cite

114

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“…We recently found that polysulfides are produced by the oxida-391 tion of H 2 S in the brain Polysulfides with varying numbers of sulfurs are produced. 396 Polysulfides induce Ca 2+ influx in astrocytes, which is approxi-397 mately 300 times more potent than parental H 2 S (Kimura et al,398 2013; Nagai et al, 2004Nagai et al, , 2006Oosumi et al, 2010). The effect of 399 polysulfides is suppressed by TRPA1 selective inhibitors, HC-400 030031 and AP-18, as well as by siRNAs selective for TRPA1, sug- Fig.…”

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confidence: 99%

Physiological role of hydrogen sulfide and polysulfide in the central nervous system

Kimura

2013

Neurochemistry International

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“…In our previous research, we found that polysulfides activate TRP channels more potently than does H 2 S (Nagai et al 2006;Oosumi et al 2010). High concentrations of NaHS (1-10 mM) activate TRPA1 channels in sensory neurons in the urinary bladder and dorsal ganglion (Streng et al 2008;Ogawa et al 2012).…”

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confidence: 88%

Physiological Roles of Hydrogen Sulfide and Polysulfides

Kimura

2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotective molecule. H2S modulates neurotransmission, regulates vascular tone, protects various tissues and organs, regulates inflammation, induces angiogenesis, and detects cellular oxygen levels. H2S is produced from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) together with cysteine aminotransferase (CAT). Recently, a novel pathway for the production of H2S from D-cysteine was identified, involving D-amino acid oxidase (DAO) together with 3MST. Sulfuration (also called sulfhydration), which adds sulfur atoms to the cysteine residues of target proteins to modify protein activity, has been extensively studied as a mode of H2S action. Recently, hydrogen polysulfides (H2Sn, where n=3-7; n=2 is termed as persulfide) have been found to sulfurate target proteins in the brain, including transient receptor potential ankyrin 1 (TRPA1) channels, Kelch-like ECH-associating protein 1 (Keap1), and phosphatase and tensin homolog (PTEN), much more potently than H2S. The physiological stimuli that trigger the production of H2S and polysulfides, and the mechanisms maintaining their local levels, remain unknown. Understanding the regulation of H2Sn (including H2S) production, and the specific stimuli that induce their release, will provide new insight into the biology of H2S and will provide novel avenues for therapeutic development in diseases involving H2S-related substances.

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Polysulfide activates TRP channels and increases intracellular Ca2+ in astrocytes

Cited by 26 publications

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

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

Physiological role of hydrogen sulfide and polysulfide in the central nervous system

Physiological Roles of Hydrogen Sulfide and Polysulfides

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