L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments

Yamane, Satoshi; Nomura, Ryouya; Yanagihara, Madoka; Nakamura, Hiroyuki; Fujino, Hiromichi; Matsumoto, Kenjiro; Horie, Syunji; Murayama, Toshihiko

doi:10.1016/j.ejphar.2015.07.042

Cited by 5 publications

(2 citation statements)

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“…The most obvious method to increase H 2 S levels in the body, of course, is by "feeding" the endogenous H 2 S producing enzymes with its substrates: L-cysteine and L-homocysteine for CSE and CBS, 3-mercaptopyruvate for 3-MST, and a-ketoglutarate for CAT (which, in turn, produces 3-MP). Although it is generally assumed that cells contain saturating concentrations of these substrates and, therefore, exogenous supplementation would not have a marked effect, in fact, in vitro and in vivo studies demonstrate that these three substrates can increase H 2 S levels, in a fashion that is reduced by inhibitors of the respective H 2 S-producing enzymes (e.g., Kartha et al, 2012;Ahn et al, 2017;, and induce biologic effects that are consistent with elevation of H 2 S production, such as smooth muscle relaxation (d'Emmanuele di Villa Bianca et al, 2009;Flannigan et al, 2013;Yamane et al, 2015;Prieto-Lloret and Aaronson, 2015;Kuo et al, 2016;Yetik-Anacak et al, 2016), cell proliferation and angiogenesis (Wang et al, 2013c;Coletta et al, 2015), organ protection (Elsey et al, 2010;Magierowski et al, 2017) and bell-shaped effects on mitochondrial function (stimulation at lower concentrations and inhibition at higher concentrations) (Modis et al, 2013a,b). In some tissues, D-cysteine can also yield H 2 S, through actions on the D-amino acid oxidase, with beneficial/cytoprotective results Souza et al, 2017).…”

Section: Alternative Means To Increase Biologic H 2 S Levelsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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Section: Alternative Means To Increase Biologic H 2 S Levelsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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“…The treatment with glibenclamide, a K ATP channel blocker, reduced both the l -cysteine response and NaHS-induced inhibition of contractions [ 166 ]. The same group later identified that inhibition of electrical field stimulation-induced contractions in ileum by l -cysteine and d,l -homocysteine was decreased by the treatment with 2-aminobicyclo [2.2.1]heptane-2-carboxylate (BCH), an inhibitor of l type and B° + transporter systems, thus highlighting the role of the amino acid transport system in l -cysteine regulation (via H 2 S) of motility [ 167 ].…”

Section: Effects Of Host-derived H 2 S On the Gmentioning

confidence: 99%

Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract

2015

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Hydrogen sulfide (H2S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H2S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H2S has been found to have pleiotropic effects on physiology and health. H2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H2S production by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H2S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H2S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn’s disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H2S on host physiology and pathophysiology.

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Altered circadian dynamics of Per2 after cystathionine-β-synthase and/or cystathionine-γ-lyase pharmacological inhibition in serum-shocked NIH-3T3 cells

Romerowicz-Misielak

Kozioł

Nowak

et al. 2021

Archives of Biochemistry and Biophysics

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L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments

Cited by 5 publications

References 54 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract

Altered circadian dynamics of Per2 after cystathionine-β-synthase and/or cystathionine-γ-lyase pharmacological inhibition in serum-shocked NIH-3T3 cells

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L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments

Cited by 5 publications

References 54 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract

Altered circadian dynamics of Per2 after cystathionine-β-synthase and/or cystathionine-γ-lyase pharmacological inhibition in serum-shocked NIH-3T3 cells

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors