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Journal ArticleDOI

Polysulfides are possible H2S-derived signaling molecules in rat brain

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TLDR
It is shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude.
Abstract
Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca(2+) influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca(2+) influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1-selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca(2+) influx, and responses to polysulfides were suppressed by TRPA1-selective inhibitors, HC-030031 and AP-18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S-derived signaling molecules that stimulate TRP channels in the brain.

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Citations
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Journal ArticleDOI

Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems

TL;DR: Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
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

Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways

TL;DR: It is posited that sulfide oxidation pathways mediate sulfide signaling and that sulfurtransferases ensure target specificity and that sulfides, polysulfides and thiosulfate generate a series of reactive sulfur species that could modify target proteins.
Journal ArticleDOI

Polysulfides Link H2S to Protein Thiol Oxidation

TL;DR: This study suggests that the effects that have been attributed to H2S in previous reports may in fact have been mediated by polysulfides, and supports the notion that sulfane sulfur rather than sulfide is the actual in vivo agent of H 2S signaling.
References
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Journal ArticleDOI

A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.

TL;DR: These findings call into question the concept of a “glial” cell class as the gene profiles of astrocyte and oligodendrocytes are as dissimilar to each other as they are to neurons, for better understanding of neural development, function, and disease.
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The possible role of hydrogen sulfide as an endogenous neuromodulator

TL;DR: It is shown that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation, suggesting that endogenous H 2S functions as a neuromodulator in the brain.
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The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener

TL;DR: It is demonstrated that H2S is an important endogenous vasoactive factor and the first identified gaseous opener of KATP channels in vascular SMCs and production from vascular tissues was enhanced by nitric oxide.
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The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide.

TL;DR: In this paper, the authors showed that mRNA for another H2S producing enzyme, cystathionine gamma-lyase, is expressed in the ileum, portal vein, and thoracic aorta.
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Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines

TL;DR: In this paper, the authors used click chemistry to show that derivatives of two such compounds, mustard oil and cinnamaldehyde, covalently bind mouse TRPA1 currents that were maintained at least 10 min after washout of the compound in calcium-free solutions.
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