Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Kimura, Hideo

doi:10.1111/bph.15246

Cited by 26 publications

(17 citation statements)

References 159 publications

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“…This enzyme is known to play a role in antioxidant and detoxification processes, and is also recognized as a source of H 2 S, polysulfides, and reactive sulfur species. These actions are relevant for the regulation of a variety of processes in the fields of neurobiology, vascular biology, and immunology. − The current project focuses on the role of 3-MST in cancer, where the H 2 S produced has been implicated in the maintenance of tumor cell bioenergetics and proliferation, in the maintenance of tumor cells in the mesenchymal (as opposed to epithelial) “state”, as well as in tumor angiogenesis. − ,, Inhibition of these processes is expected to exert antitumor effects (on its own, or possibly in combination with anticancer agents with different molecular targets). The current results, indeed, support this concept.…”

Section: Resultsmentioning

confidence: 99%

Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer

et al. 2021

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The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST’s active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.

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Section: Resultsmentioning

confidence: 99%

Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer

et al. 2021

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“…H 2 S is recognized as a key molecule with a signaling function in animal and plant cells, with similar regulatory properties to those exerted by nitric oxide (NO) in higher plants under physiological and stress conditions [ 9 , 33 , 34 , 35 , 36 , 37 , 38 ]. With the aim of obtaining a better understanding of this molecule in different plants with agronomic interest, the endogenous content, its emission, as well as its possible correlation with LCD activity have been comparatively studied, since it is considered the most relevant enzyme in the H 2 S production in plant cells.…”

Section: Discussionmentioning

confidence: 99%

H2S in Horticultural Plants: Endogenous Detection by an Electrochemical Sensor, Emission by a Gas Detector, and Its Correlation with L-Cysteine Desulfhydrase (LCD) Activity

Muñoz‐Vargas

González‐Gordo

Palma

et al. 2022

IJMS

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H2S has acquired great attention in plant research because it has signaling functions under physiological and stress conditions. However, the direct detection of endogenous H2S and its potential emission is still a challenge in higher plants. In order to achieve a comparative analysis of the content of H2S among different plants with agronomical and nutritional interest including pepper fruits, broccoli, ginger, and different members of the genus Allium such as garlic, leek, Welsh and purple onion, the endogenous H2S and its emission was determined using an ion-selective microelectrode and a specific gas detector, respectively. The data show that endogenous H2S content range from pmol to μmol H2S · g−1 fresh weight whereas the H2S emission of fresh-cut vegetables was only detected in the different species of the genus Allium with a maximum of 9 ppm in garlic cloves. Additionally, the activity and isozymes of the L-cysteine desulfhydrase (LCD) were analyzed, which is one of the main enzymatic sources of H2S, where the different species of the genus Allium showed the highest activities. Using non-denaturing gel electrophoresis, the data indicated the presence of up to nine different LCD isozymes from one in ginger to four in onion, leek, and broccoli. In summary, the data indicate a correlation between higher LCD activity with the endogenous H2S content and its emission in the analyzed horticultural species. Furthermore, the high content of endogenous H2S in the Allium species supports the recognized benefits for human health, which are associated with its consumption.

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“… 78 , 90 , 91 Cysteine S-nitrosylation and S-sulfination are endogenously occurring post-translational modifications of proteins. Such S-nitrosylated or S-sulfinated Cys residues can be S-sulfurated by H 2 S. 92 , 93 …”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Upregulates Acid-sensing Ion Channels via the MAPK-Erk1/2 Signaling Pathway

Peng

Kellenberger

2021

Function

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Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of extracellular signal-regulated kinase, which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as e.g. facilitation of learning and memory, protection during seizure activity and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.

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Hydrogen sulfide signalling in the CNS ‐ Comparison with NO

Cited by 26 publications

References 159 publications

Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer

Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer

H2S in Horticultural Plants: Endogenous Detection by an Electrochemical Sensor, Emission by a Gas Detector, and Its Correlation with L-Cysteine Desulfhydrase (LCD) Activity

Hydrogen Sulfide Upregulates Acid-sensing Ion Channels via the MAPK-Erk1/2 Signaling Pathway

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