Action Of H2S Research Articles

Ethylene-Induced Hydrogen Sulfide Negatively Regulates Ethylene Biosynthesis by Persulfidation of ACO in Tomato Under Osmotic Stress.

A number of recent studies identified hydrogen sulfide (H2S) as an important signal in plant development and adaptation to environmental stress. H2S has been proven to participate in ethylene-induced stomatal closure, but how the signaling pathways of H2S and ethylene interact is still unclear. Here, we reveal how H2S controls the feedback-regulation of ethylene biosynthesis in tomato (Solanum lycopersicum) under osmotic stress. We found that ethylene induced the production of H2S in guard cells. The supply of hypotaurine (HT; a H2S scavenger) or DL-pro-pargylglycine (PAG; a synthetic inhibitor of H2S) removed the effect of ethylene or osmotic stress on stomatal closure. This suggests that ethylene-induced H2S is a downstream component of osmotic stress signaling, which is required for ethylene-induced stomatal closure under osmotic stress. We further found that H2S inhibited ethylene synthesis through inhibiting the activity of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidases (ACOs) by persulfidation. A modified biotin-switch method (MBST) showed that H2S can induce persulfidation of LeACO1 and LeACO2 in a dose-dependent manner, and that persulfidation inhibits the activity of LeACO1 and LeACO2. We also found that LeACO1 is persulfidated at cysteine 60. These data suggested that ethylene-induced H2S negatively regulates ethylene biosynthesis by persulfidation of LeACOs. In addition, H2S was also found to inhibit the expression of LeACO genes. The results provide insight on the general mode of action of H2S and contribute to a better understanding of a plant’s response to osmotic stress.

Interaction between Hydrogen Sulfide and Muscarinic Receptors in the Regulation of Contractility of the Mouse Atrium

Hydrogen sulfide (H2S) is an endogenously synthesized gaseous transmitter that participates in the regulation of the cardiovascular system and has a cardioprotective effect under ischemia–reperfusion conditions. Here, we studied possible mechanisms of the interaction of H2S and muscarinic acetylcholine receptors in the regulation of mice atrium contractility in the isometric conditions. We show that sodium hydrosulfide (NaHS), an exogenous donor of H2S, caused dose-dependent and reversible depression of the contractile force in the concentration range from 1 μM to 5 mM. The negative inotropic effect of NaHS did not change after the activation of muscarinic acetylcholine receptors by carbachol. However, we observed that the negative inotropic effect of carbachol increased after preliminary application of NaHS. The application of the reducing agent dithiothreitol did not change the effects of carbachol, which indicated that the effects of NaHS was not related to a direct action on the disulfide bonds of the receptor’s protein subunits. The increased effects of carbachol after NaHS application were not prevented by the inhibition of intracellular signaling pathway that mediated activation of M-cholinergic receptors, including adenylate cyclase, guanylate cyclase, and NO-synthase. However, an increase in the carbachol negative inotropic effect was not observed when ATP-dependent potassium channels were inhibited by glibenclamide. In its turn, activation of ATPdependent potassium channels by diazoxide resulted in an increase in carbachol negative inotropic action in the atrial myocardium of mice similar to the effect of NaHS. Our data indicate that the enhanced negative inotropic effect of carbachol under the action of H2S in the mouse atrium was mediated by the activation of ATP-dependent potassium channels.

Interaction of the hydrogen sulphide inhibitor, propargylglycine (PAG), with hydrogen sulphide on postharvest changes of the green leafy vegetable, pak choy

Propargylglycine (PAG) is an inhibitor of hydrogen sulphide (H2S) production and has been used to explore the mode of action of H2S in prolonging storage of horticultural produce but little attention has been given to how PAG and H2S interact when both are applied to produce. This study examined the effect of sequential application of PAG and H2S on a range of postharvest senescence factors of the leafy vegetable pak choy (Brassica rapa subsp. Chinensis) stored at 10 °C. The results showed differential responses between factors when compared to application of PAG or H2S alone. As expected, fumigation with H2S reduced the rate of loss of leaf green colour, respiration rate, ethylene production, ion leakage and enhanced antioxidant activity and leaves sprayed with PAG showing converse effects. If PAG acted solely by inhibiting endogenous H2S production then subsequent treatment with H2S should fully negate any effect induced by PAG. However, for the combined PAG + H2S treatment, respiration was similar leaves fumigated with H2S, loss of green leaf colour was similar to the PAG single treatment and less than the untreated control, antioxidant activity was less than for PAG but greater than for control leaves, and ethylene production and ion leakage were similar to control leaves. Thus, the concept that PAG is exclusively an inhibitor of endogenous H2S production was not validated, with PAG having effects on metabolism that are not linked to the action of endogenous H2S. The additional actions of PAG could be through its inhibition of pyridoxyal-5′-phosphate (PHP) which is a coenzyme for numerous enzyme systems.

Hydrogen Sulfide (H2S)-Releasing Compounds: Therapeutic Potential in Cardiovascular Diseases.

Cardiovascular disease is the main cause of death worldwide, but its pathogenesis is not yet clear. Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in the organism after carbon monoxide and nitric oxide. It can be synthesized in mammalian tissues and can freely cross the cell membrane and exert many biological effects in various systems including cardiovascular system. More and more recent studies have supported the protective effects of endogenous H2S and exogenous H2S-releasing compounds (such as NaHS, Na2S, and GYY4137) in cardiovascular diseases, such as cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and atherosclerosis. Here, we provided an up-to-date overview of the mechanistic actions of H2S as well as the therapeutic potential of various classes of H2S donors in treating cardiovascular diseases.

A novel role of sONE/NOS3/NO signaling cascade in mediating hydrogen sulphide bilateral effects on triple negative breast cancer progression

Hydrogen sulphide (H2S) gas has been recognized as an intracellular mediator influencing an array of signaling pathways. Yet, the role of H2S in cancer progression has been controversial. This study aims to unravel the role of exogenous H2S in triple negative breast cancer (TNBC) and to further investigate any possible association of H2S mediated actions with the endogenous production of nitric oxide (NO) gas. A wide concentration range of NaHS (20–2000 μM) and a variable reaction time (2–72 h) were probed. A bell-shaped impact of H2S on TNBC cellular viability, proliferation, migration, invasion and colony forming ability was repeatedly observed in the aggressive TNBC cell lines, MDA-MB-231 but not in hormone receptor positive, MCF-7 cells. This bell-shaped effect was found to be shifted towards the left upon increasing the reaction time within the range of 2–24 h. However, this was totally opposed in case of continuous exposure (72 h) to exogenous H2S. An inverted bell-shaped effect of H2S on TNBC cellular growth, migration, proliferation and colony forming ability was shown. Moreover, this study provided the first evidence of a possible involvement of NO in mediating H2S actions in TNBC. Such intricate cross-talk was found to be orchestrated by the novel lncRNA, sONE and its down-stream target NOS3 building up a novel axis, sONE/NOS3/NO, that was shown to play a pivotal role in plotting the bilateral effect of H2S on TNBC progression. Finally, this study showed that low and continuous exposure of H2S serves as a novel, selective and effective strategy in harnessing TNBC oncogenic profile through cGMP dependent and independent pathways where alterations of cell cycle regulatory proteins such as TP53 and c-Myc was observed. Moreover, NaHS could repress TNBC migration and invasion capacities through repressing the intracellular adhesion molecule, ICAM-1. In conclusion, this study provides an insight about the role of exogenous H2S in TNBC cell lines highlighting a novel crosstalk between H2S and NO orchestrated by sONE/NOS3 axis.

Role of Nitric Oxide and Hydrogen Sulfide in Ischemic Stroke and the Emergent Epigenetic Underpinnings.

Nitric oxide (NO) and hydrogen sulfide (H2S) are the key gasotransmitters with an imperious role in the maintenance of cerebrovascular homeostasis. A decline in their levels contributes to endothelial dysfunction that portends ischemic stroke (IS) or cerebral ischemia/reperfusion (CI/R). Nevertheless, their exorbitant production during CI/R is associated with exacerbation of cerebrovascular injury in the post-stroke epoch. NO-producing nitric oxide synthases are implicated in IS pathology and their activity is regulated, inter alia, by various post-translational modifications and chromatin-based mechanisms. These account for heterogeneous alterations in NO production in a disease setting like IS. Interestingly, NO per se has been posited as an endogenous epigenetic modulator. Further, there is compelling evidence for an ingenious crosstalk between NO and H2S in effecting the canonical (direct) and non-canonical (off-target collateral) functions. In this regard, NO-mediated S-nitrosylation and H2S-mediated S-sulfhydration of specific reactive thiols in an expanding array of target proteins are the principal modalities mediating the all-pervasive influence of NO and H2S on cell fate in an ischemic brain. An integrated stress response subsuming unfolded protein response and autophagy to cellular stressors like endoplasmic reticulum stress, in part, is entrenched in such signaling modalities that substantiate the role of NO and H2S in priming the cells for stress response. The precis presented here provides a comprehension on the multifarious actions of NO and H2S and their epigenetic underpinnings, their crosstalk in maintenance of cerebrovascular homeostasis, and their "Janus bifrons" effect in IS milieu together with plausible therapeutic implications.

Induction of inactive TGF-β1 monomer formation by hydrogen sulfide contributes to its suppressive effects on Ang II- and TGF-β1-induced EMT in renal tubular epithelial cells

Hydrogen sulfide (H2S), an endogenous gas mediator with multifaced biological functions, has been shown to be effective in the prevention and treatment of renal sclerosis in several models of chronic renal diseases. The mechanisms involved are still unclear. Given that Ang II- and TGF-β-induced renal tubular epithelial-mesenchymal transition (EMT) is a pivotal cellular event leading to renal sclerosis, we examined whether and how H2S intervened the processes of EMT. Ang II stimulated EMT in renal tubular epithelial cells, as indicated by the increased level of α-smooth muscle actin and a decreased level of E-cadherin. This effect of Ang II was blocked by a TGF-β receptor kinase inhibitor, indicative of a mediating role of TGF-β. Consistently, Ang II stimulated TGF-β activation and addition of the exogenous TGF-β1 also induced EMT. In the presence of H2S donor NaHS, the EMT-promoting actions of Ang II and TGF-β1 were abolished, which was associated with a reduced TGF-β activity. Further analysis using a human recombinant active TGF-β1 revealed that H2S cleaved the disulfide bond in the dimeric active TGF-β1 and promoted the formation of inactive TGF-β1 monomer. Collectively, these results indicate that H2S counteracted Ang II- and TGF-β1-induced EMT through mechanisms involving direct inactivation of TGF-β1. Our study thus provides novel mechanistic insight into the anti-fibrotic actions of H2S and suggest that H2S could be used to treat renal sclerotic diseases.

P-274 - Nitrosopersulfide (SSNO­) is a potential protein Cys polysulfidating agent with sustained and long-range effects

The biological actions of NO and H2S are intimately intertwined. Chemical interactions of these molecules form a network of cascading chemicals. SSNO­ is a major product of these interactions. It is relatively stable under physiological conditions and not reducible by thiols. Upon slow decomposition of SSNO­, the sulfane sulfur equivalents are released in the form of inorganic polysulfides (HSx­). HSx­ were shown to be important mediators in H2S biology by inducing protein Cys persulfidation. However, HSx­ are readily reduced by the glutathione and thioredoxin systems inside the cell. Importantly, we found that SSNO­ can escape these reducing machineries and hence we hypothesize that it could serve as a sulfane sulfur carrier for sustained and long range HSx­ bioavailability. SSNO­ indeed induced delayed polysulfidation on Cys, GSH, HSA and a slow flux of sulfane sulfur production in HEK 293 cells. Furthermore, HSx­ were shown to activate TRPA1 channels and our experiments revealed that SSNO­ can also function as a TRPA1 activator, but with a lasting effect. These observations give credence to our hypothesis that SSNO­ may be responsible for sustained protein Cys‒polysulfidation and potentially involved in sulfane sulfur trafficking between subcellular compartments.

Dynamic redox cycling of hydrogen sulfide and polysulfide species could represent an important regulatory element in sulfur biology

The biochemical actions of Reactive Sulfur Species (RSS) are in the focus of redox signaling studies. Following the rapidly rising attention to the biological actions of H2S, in recent years an increasing number of investigations emphasize the significance of polysulfide species in sulfur biology. It is now widely accepted that polysulfides are highly abundant in biological systems with fundamental physiological and pathophysiological roles. The understanding of polysulfide producing enzymatic and non-enzymatic pathways is rapidly evolving. In addition, we demonstrated that the thioredoxin and glutathione systems can efficiently reduce inorganic and Cys-polysulfides via a number of different pathways. Beside the enzymatic interconversion of RSS, delicate speciation equilibria exist between the different forms of these species. Our mechanistic studies emphasize the fact that sulfide and polysulfides are indeed dynamically redox cycling species, which we propose should be an important regulatory element in sulfur biology.

BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress.

Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors.

A Hydrogen Sulfide Donor, JK1, Preserves Endothelial Function and Improves Exercise Capacity in Pressure Overload ‐ Induced Heart Failure

Background and HypothesisHydrogen sulfide (H2S) protects against heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. At present there is a lack of data demonstrating the protective actions of H2S in the late stages of heart failure. And the effects of H2S on exercise intolerance, the clinical hallmark of heart failure, has not been evaluated in preclinical models. In current study, we tested the efficacy of delayed therapy with a novel H2S donor, JK1, on cardiac function, endothelial function, and exercise capacity in a murine model of pressure overload‐induced heart failure.MethodsMale C57/BL6J mice at 10 weeks (wks) of age were subjected to transverse aortic constriction (TAC) for 18 weeks. JK1 (200 μg/kg/d, n=20) or the H2S deficient control compound (200 μg/kg/d, n=18) was administered via i.p. injection twice per day starting at 10 wks post TAC, in which time all mice had EF lower than 45%. Echocardiography was performed at baseline and tri‐weekly to assess LV structure and function. LV hemodynamics, cardiac fibrosis, vascular reactivity (isolated thoracic aorta), and exercise capacity were measured at the endpoint, 18 wks post TAC.ResultsDelayed treatment with JK1 initiated at 10 wks post TAC reduced LV dilation (p < 0.01) and attenuated eccentric hypertrophy (p < 0.01). However, no significant difference was noted in LV ejection fraction and cardiac fibrosis. JK1 treated mice displayed lower LV end‐diastolic pressure (LVEDP 17.8 ± 1.8 mmHg vs. 22.9 ± 1.23 mmHg, p < 0.05) and improved relaxation time constant (Tau 8 ± 0.27 ms vs. 10.05 ± 0.58 ms, p < 0.01). In addition, aortic vasorelaxation in response to acetylcholine treatment was markedly improved in mice received JK1 treatment (Max. Relaxation 51.8 ± 4.2% vs. 31.5 ± 3.6%, p < 0.01). More importantly, mice received JK1 treatment exhibited improved exercise capacity (Distance 312 ± 13.4 m vs. 89 ± 6.3 m, p < 0.05) as compared to those received control.ConclusionThese results demonstrate that delayed administration of a novel H2S donor, JK1, improves exercise capacity in severe heart failure following TAC. JK1 treatment initiated at 10 weeks post TAC did not improve systolic function or reduce cardiac fibrosis, suggesting that the beneficial effects of 10‐wks‐delayed H2S therapy in pressure overload heart failure are a result of the improved vascular function and LV hemodynamics.Support or Funding Information

Few-Layer MoS₂ Nanodomains Decorating TiO₂ Nanoparticles: A Case Study for the Photodegradation of Carbamazepine.

S-doped TiO2 and hybrid MoS2/TiO2 systems have been synthesized, via the sulfidation with H2S of the bare TiO2 and of MoOx supported on TiO2 systems, with the aim of enhancing the photocatalytic properties of TiO2 for the degradation of carbamazepine, an anticonvulsant drug, whose residues and metabolites are usually inefficiently removed in wastewater treatment plants. The focus of this study is to find a relationship between the morphology/structure/surface properties and photoactivity. The full characterization of samples reveals the strong effects of the H2S action on the properties of TiO2, with the formation of defects at the surface, as shown by transmission electron microscopy (TEM) and infrared spectroscopy (IR), while also the optical properties are strongly affected by the sulfidation treatment, with changes in the electronic states of TiO2. Meanwhile, the formation of small and thin few-layer MoS2 domains, decorating the TiO2 surface, is evidenced by both high-resolution transmission electron microscopy (HRTEM) and UV-Vis/Raman spectroscopies, while Fourier-transform infrared (FTIR) spectra give insights into the nature of Ti and Mo surface sites. The most interesting findings of our research are the enhanced photoactivity of the MoS2/TiO2 hybrid photocatalyst toward the carbamazepine mineralization. Surprisingly, the formation of hazardous compounds (i.e., acridine derivatives), usually obtained from carbamazepine, is precluded when treated with MoS2/TiO2 systems.

Beneficial Role of Hydrogen Sulfide in Renal Ischemia Reperfusion Injury in Rats.

PurposeHydrogen sulfide (H2S) is an endogenous gaseous molecule with important physiological roles. It is synthesized from cysteine by cystathionine γ-lyase (CGL) and cystathionine β-synthase (CBS). The present study examined the benefits of exogenous H2S on renal ischemia reperfusion (IR) injury, as well as the effects of CGL or CBS inhibition. Furthermore, we elucidated the mechanism underlying the action of H2S in the kidneys.Materials and MethodsThirty male Sprague-Dawley rats were randomly assigned to five groups: a sham, renal IR control, sodium hydrosulfide (NaHS) treatment, H2S donor, and CGL or CBS inhibitor administration group. Levels of blood urea nitrogen (BUN), serum creatinine (Cr), renal tissue malondialdehyde (MDA), and superoxide dismutase (SOD) were estimated. Histological changes, apoptosis, and expression of mitogen-activated protein kinase (MAPK) family members (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) were also evaluated.ResultsNaHS attenuated serum BUN and Cr levels, as well as histological damage caused by renal IR injury. Administration of NaHS also reduced oxidative stress as evident from decreased MDA, preserved SOD, and reduced apoptotic cells. Additionally, NaHS prevented renal IR-induced MAPK phosphorylation. The CGL or CBS group showed increased MAPK family activity; however, there was no significant difference in the IR control group.ConclusionExogenous H2S can mitigate IR injury-led renal damage. The proposed beneficial effect of H2S is, in part, because of the anti-oxidative stress associated with modulation of the MAPK signaling pathways.

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy

Hydrogen sulfide (H2S) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina. Studies of the pharmacological actions of H2S (using several compounds as fast- and slow-releasing gas donors) on anterior uveal tissues reveal an effect on sympathetic neurotransmission and the ability of the gas to relax precontracted iris and ocular vascular smooth muscles, responses that were blocked by inhibitors of CSE, CBS, and KATP channels. In the retina, there is evidence that H2S can inhibit excitatory amino acid neurotransmission and can also protect this tissue from a wide variety of insults. Furthermore, exogenous application of H2S-releasing compounds was reported to increase aqueous humor outflow facility in an ex vivo model of the porcine ocular anterior segment and lowered intraocular pressure (IOP) in both normotensive and glaucomatous rabbits. Taken together, the finding that H2S-releasing compounds can lower IOP and can serve a neuroprotective role in the retina suggests that H2S prodrugs could be used as tools or therapeutic agents in diseases such as glaucoma.

Characterizing Physiological and Proteomic Analysis of the Action of H2S to Mitigate Drought Stress in Young Seedling of Wheat

Hydrogen sulfide (H2S) is a gaseous signaling molecule that has been shown to improve drought resistance in plants. In this study, comparative physiological and proteomic analyses were performed to investigate the underlying mechanism by which H2S alleviates drought stress in wheat seedlings. Pretreatment with sodium hydrosulfide (NaHS), an H2S donor, significantly increased height and decreased lipid peroxidation levels in wheat seedlings under drought stress. The antioxidant levels (ascorbate and reduced glutathione), and the contents of starch and soluble sugars were all increased in plants pretreated with NaHS. Using the iTRAQ (isobaric tags for relative and absolute quantitation) technique, 120 proteins were found to be significantly regulated by NaHS under drought stress (57 increased and 63 decreased) compared with drought treatment without NaHS. Functional annotation showed that these proteins are mainly related to carbohydrate metabolism, photosynthesis, signal transduction, protein synthesis, stress, and secondary metabolism. Nine proteins were selected to examine the transcriptional levels of their corresponding genes, and most of them displayed expression patterns similar to the proteomic profiles. These results show that H2S can alleviate drought stress in wheat seedlings by regulating multiple biochemical pathways and that energy and carbon metabolism, signal transduction, antioxidant capacity, and protein synthesis may play important roles in the regulation of drought stress in plants.

An Update on AMPK in Hydrogen Sulfide Pharmacology.

Hydrogen sulfide (H2S), the third bio-active gasotransmitter, is produced endogenously and tightly involved in the pathogenesis and treatment for various diseases. Adenosine 5′-monophosphate-activated protein kinase (AMPK) plays a paramount role in maintaining cellular energetic balance. Increasing evidences have also suggested AMPK as a novel modulator in multiple pathological conditions. In this paper, we will review the biological principles of H2S and AMPK, and most importantly, the recent discoveries regarding AMPK-mediated pharmacological actions of H2S. Emphasis will be laid on AMPK/H2S interactions in the cardiovascular system, autophagy, diabetic complications, and inflammation. In most cases described in this article, by promoting AMPK activation, H2S exerts cytoprotective effects or therapeutic potentials, though there remain some controversies before we can fully understand the involved mechanisms. Further researches are in need to investigate more closely any relationship between H2S and AMPK, and to put forward the development of H2S donors for clinical application.

Hydrogen Sulfide Inhibits Antibody- and complement-mediated Immune Responses via S-sulfhydration

Hydrogen sulfide (H2S) has emerged as an important biological mediator with numerous pathophysiological roles. One of the well-reported actions of H2S is to inhibit immune responses. However, most of the results are obtained from studies on cellular immunity. Currently, little information is available regarding its role in humoral immunity. Given that the effector molecules in humoral immunity, such as antibody and complement, contain abundant disulfide bonds, we speculated that H2S might regulate their function via S-sulfhydration. Here, we addressed this possibility. Exposure of monoclonal anti-Thy-1 antibody to structurally different H2S donors (NaHS, Na2S and GYY4137) resulted in a marked reduction in antibody binding to the thy-1 molecules in thymus T cells and mesangial cells. This effect of H2S donors was weakened by preincubation of the donors with medium for 24 h, indicative of an effect of H2S. Besides, H2S potently prevented the antibody-mediated agglutination of red blood cells, aggregation of antibody-sensitized microspheres, and anti-CD95-induced cell apoptosis in Jurkat T cells. Further analysis revealed that H2S caused antibody S-sulfhydration. Moreover, H2S significantly suppressed the classic and alternative complement activation pathways. Like H2S, thiol-reactive antioxidant GSH and NAC also potently suppressed antibody- and complement-mediated immune responses via disruption of disulfide bonds. Collectively, our results revealed, for the first time, that H2S inhibits humoral immune responses via reduction of disulfide bonds in the effector molecules. Our study thus provides novel mechanistic insights into the immunosuppressive actions of H2S and suggests that it might be used to treat certain immune disorders.

Neuroprotective effects of hydrogen sulfide on sodium azide-induced oxidative stress in PC12 cells.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, responsible for >50% of all dementia cases. Sodium azide (NaN3) inhibits cytochrome oxidase by irreversibly binding to the heme cofactor and selectively reducing the complex IV activity, which is present in post-mortem AD brains. Previous data demonstrated that hydrogen sulfide (H2S), the third endogenous gaseous mediator, exerted protective effects against neuronal damage. Therefore, it was hypothesized that H2S may be able to scavenge excess reactive oxygen species (ROS), thereby protecting against oxidative stress and cell death. In the present study, it was observed that cell viability decreased in a concentration-dependent manner 12 h after NaN3 treatment (20, 30 and 50 mmol/l). A decrease in cell viability (to 51±3%) was observed 12 h after treatment with 30 mM NaN3. NaN3 treatment also led to decreased mitochondrial membrane potential, increased lipid peroxidation (excessive production of malondialdehyde), and increased the protein expression levels of caspase-3. Pretreatment with H2S (200 μmol/l) attenuated NaN3-mediated apoptosis, and the anti-apoptotic action of H2S was partially dependent on suppressing the production of ROS. The findings of the present study suggested that H2S exerted a neuroprotective effect against NaN3-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis. Therefore, the findings of the present study suggest there may be a promising future for H2S-based preventions and therapies for neuronal damage following exposure to NaN3.

Trace compounds impact on SOFC performance: Experimental and modelling approach

Issues related to SOFCs performance and durability are strictly dependent on the feeding fuel quality. SOFC capability to be fed with fuels different from hydrogen opens to scenarios in which a big variety of fuels can be used at the aim. Unfortunately, problems related to anode deactivation due to the contaminants presence can arise. The present work investigates the performance of anode supported solid oxide fuel cells in case of co-feeding of different trace compounds. Electrochemical impedance spectroscopy is the investigation technique used to analyze the impedance spectra. Typical biogas from OFMSW trace contaminants that follow an initial failure in the cleaning system, such as sulphur, aromatic compounds and siloxanes, have been simultaneously tested. Tests showed that the most deleterious impact for the SOFC was due to the H2S action. This influences mostly the electrochemical losses respect to diffusion losses, even if this last are not null and can be accounted as a secondary effect. On the contrary, the co-presence of D4 and H2S mitigates in the short-term the effect that the only D4 produces when fed with biogas. The most relevant consequence produced by C7H8 was recorded in the low frequency of Nyquist plot, affecting mainly the mass transport phenomena. Experimental tests are accompanied by the implementation of the fuel cell model through COMSOL Multiphysics software to study the effect of pollutants on fuel cell performance.

H2S is a key antisecretory molecule against cholera toxin-induced diarrhoea in mice: Evidence for non-involvement of the AC/cAMP/PKA pathway and AMPK

Hydrogen sulphide (H2S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl− induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of H2S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H2S. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the H2S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H2S donors. H2S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H2S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.