Search

Hydrogen sulfide (H(2)S) together with polysulfides (H(2)S(n), n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H(2)S and H(2)S(n) diffuse to the target proteins for S‐sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3‐mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3‐mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S‐nitrosylation. S‐sulfuration and S‐nitrosylation by enzymes proceed only inside the cell, while reactions induced by H(2)S, H(2)S(n) and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S‐sulfuration and S‐nitrosylation causes many nervous system diseases. This review focuses on the signalling by H(2)S and H(2)S(n) with S‐sulfuration comparing to that of NO with S‐nitrosylation and discusses on their roles in physiology and pathophysiology.

Background and purpose Hydrogen sulfide (H2 S) and polysulfides (H2 Sn ) are signalling molecules that mediate various physiological responses including cytoprotection. Their oxidized metabolite sulfite (SO3 2- ) is found in blood and tissues. However, its physiological role remains unclear. In this study, we investigated the cytoprotective effect of sulfite on neurons exposed to oxidative stress caused by high concentrations of the neurotransmitter glutamate, known as oxytosis. Experimental approach Concentrations of sulfite as well as those of cysteine and GSH in rats were measured by HPLC. Cytoprotective effects of sulfite on primary cultures of rat neurons against oxytosis was examined by WST-8 cytoprotective and LDH cytotoxicity assays and compared with that of H2 S, H2 Sn and thiosulfate. Key results Free sulfite, present at approximately 2 μM in the rat brain, converts cystine to cysteine more efficiently than H2 S and H2 Sn and facilitates transport of cysteine into cells. Physiological concentrations of sulfite protected neurons from oxytosis and were accompanied by increased intracellular concentrations of cysteine and GSH probably due to converting extracellular cystine to cysteine, more efficiently than H2 S and H2 Sn . In contrast, thiosulfate only slightly protected neurons from oxytosis. Conclusions and implications Our present data have shown sulfite to be a novel cytoprotective molecule against oxytosis, through maintaining cysteine levels in the extracellular milieu, leading to increased intracellular cysteine and GSH. Although there may be adverse clinical effects in sensitive individuals, our results provide a new insight into the therapeutic application of sulfite to neuronal diseases caused by oxidative stress. Linked articles This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.

Schizophrenia is a complex, multifactorial disease that displays heterogeneous behavioral and cognitive syndrome (Lieberman & First, 2018). The origin of schizophrenia appears to lie in genetic and/or environmental disruption of brain development (Owen et al, 2016). In spite of current treatment that largely consists in antipsychotic drugs combined with psychological therapies, social support, and rehabilitation, developing more effective therapeutic interventions is an essential issue., What if energy metabolism dysregulation was a pathomechanism underlying schizophrenia? Ide et al (2019) identify sulfide stress as a new player in this disorder.

For practical application, the functional piezoelectric film in microelectromechanical systems should meet the requirement of physical properties, as well as the mechanical properties. In this article, 0.5Ba(Ti0.8Zr0.2)O3–0.5(Ba0.7Ca0.3)TiO3 (0.5BZT–0.5BCT) thin films with varied properties were prepared on (100) Si substrates via a sol–gel technique at different annealing temperatures. The effects of the annealing temperature on the morphology, piezoelectricity, hardness, and elastic modulus were studied. Particular attention was paid to the surface frictional behavior of films, and the changes in the friction force can be radically explained in terms of differences in the hardness/elastic modulus ratio and the residual stress of films. And, it reveals that the higher ratio of hardness to elastic modulus and tensile residual stress can contribute to a lower friction force for 0.5BZT–0.5BCT film during sling friction.

Overexpression of high mobility group AT-hook 2 (Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3'-untranslated region (3'UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3'UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3'UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34(+) cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34(+) cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/HMGA2 axis could be a therapeutic target in MPNs.

Polysulfide is a bound sulfur species derived from endogenous H2S. When mouse neuroblastoma, Neuro2A cells were exposed to tert-butyl hydroperoxide after treatment with polysulfide, a significant decline in cell toxicity was observed. Rapid uptake of polysulfides induced translocation of Nrf2 into the nucleus, resulting in acceleration of GSH synthesis and HO-1 expression. We demonstrated that polysulfide reversibly modified Keap1 to form oxidized dimers and induced the translocation of Nrf2. Moreover, polysulfide treatment accelerated Akt phosphorylation, which is a known pathway of Nrf2 phosphorylation. Thus, polysulfide may mediate the activation of Nrf2 signaling, thereby exerting protective effects against oxidative damage in Neuro2A cells.

Questions: How does the severity of prescribed fires affect vegetation and seed bank in a wetland? Location: A fire-prone reed swamp in northern Japan (250 ha, 40°49′N, 141°22′E, 30 000 seeds m−2 throughout all the treatments. Perennial plants were dominant in the vegetation, while annuals, biennials and rushes were dominant in the seed bank. Small seeds were more abundant in the soil than in the litter. Qualitative and quantitative similarities between seed bank and the vegetation were low, and tended to be higher in H. Conclusions: Fire contributed to the development of diverse standing vegetation via the positive effects on seed bank dynamics, and can be considered a tool to maintain species-rich marshes.

Alkali metals (Na, Rb or Cs) co-doped with fiber- and bulk-shaped KNbO3 single crystals were grown using two original methods by means of doping together of small ionic Na and large ionic Rb or Cs into KNbO3. Single-phase crystals could be grown with an orthorhombic system at room temperature as well as pure KNbO3. Piezoelectric and ferroelectric property changes by the co-doping of Rb or Cs with Na were estimated using d33 values and a polarization-electric field hysteresis curve in fiber- and bulk-shaped crystals. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We have demonstrated a synthetic procedure for nano-sized NaNbO3 powder and its thin films using a carbon-free precursor prepared by the reaction of H2O2 with sodium and niobium alkoxides. A combination of X-ray powder diffraction, Raman spectra, and thermal gravity and differential thermal analysis, carbon analysis, fourier transform infrared spectra, transmission electron microscopy, and atomic force microscopy was used to characterize the resulting materials and precursor compounds. Results show that this procedure demonstrates the major advantages of low-temperature synthesis (∼400°C) and low weight loss during transformation into NaNbO3 because of its carbon-free nature, which also provides the option of preparing nano-sized particles and dense, crack-free NaNbO3 thin films.

A wide-gap (up to 30 mm) radio frequency (RF) glow discharge was realized at atmospheric pressure, using soft X-ray photo-emission, pre-ionization. The RF glow plasma was excited with an automated matching system, at industrial frequencies (13.56 and 27.12 MHz), in helium or helium-diluted oxygen. Antibacterial effects were examined using spore-forming bacteria: Bacillus atrophaeus, Bacillus subtilis, Geobacillus steamthennophilus, Bacillus pumilis, and selected species of bacteria, a mold, and a yeast-like fungus; Pseudomonas aeroginosa, Salmonella enteritidis, Enterobactor aerogenes, Lactobacillus plantarum, Staphylococcus aureus, Candida albicans, and Aspergillus niger.

Crystals listed in the JCPDS card in BaO-B2O3-Al2O3 and BaO-B2O3-Ga2O3 systems were synthesized by means of a solid-state reaction method and a liquid-state reaction method. Synthesized crystals were characterized from a viewpoint of Second Harmonic Generation (SHG) and crystal growth possibility. Ba5Al4B12O29 and Ba5Ga4B12O29 are promising new candidate crystals from the viewpoint of SHG activity and congruent melting behavior. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Fluctuation of crystallization was observed at floating molten zone under reduced gravity condition on airplane. The zone material was Ba(B0.9Al0.1)2O4. A pair of Pt tubes was used at the upper and the lower positions, and the molten zone was formed between two Pt tubes. Double peak temperature profile could be performed using two Pt tubes. Crystallization of the molten Ba(B0.9Al0.1)2O4 was started at center part of side surface of floating molten zone under reduced gravity condition. The formed crystal was melted again during the crystallization by the gravity fluctuation at the center part of the floating molten zone. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Crystals listed in the JCPDS card in the BaO-B2O3-Al2O3 and BaO-B2O3-Ga2O3 systems are of interest from a viewpoint of the Second Harmonic Generation (SHG). Ba5Al4B12O29 and Ba5Ga4B12O29 are promising new crystals with SHG activity and with congruent melting mode. These crystals can be grown by the Czochralski method with a size of 3 × 3 × 0.1-1mm. (© 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Amyloid beta protein (A beta), which accumulates in the senile plaques in the brain of Alzheimer's patients, is cytotoxic to neurons. A modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, in which a yellow redox dye, MTT, is reduced to purple formazan, is very sensitive to the effect of A beta. In primary hippocampal cultures, inhibition of MTT reduction starts within 2 h after the addition of low concentrations of A beta and reaches a plateau in 12 h. This effect of A beta is not blocked by Ca2+ channel blockers or in Ca(2+)-free medium. In contrast, lactate dehydrogenase (LDH) release and trypan blue exclusion, which are indices of cell death, start 3 days after exposure to high concentrations of A beta and are blocked by Ca2+ channel blockers such as Co2+, nicardipine, and diltiazem. When A beta was washed out from the medium after 12 h, MTT reduction recovers and LDH release does not occur, suggesting that a long-lasting inhibition of the cellular redox system may be required to induce cell death. These observations demonstrate that A beta toxicity consists of two phases-a Ca(2+)-independent early phase and a Ca(2+)-dependent late phase- and that the early phase may be required to induce the late phase.

Hydrogen sulfide (H2S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine beta-synthase (CBS) and functions as a neuromodulator in the brain. H2S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP). The production of H2S is regulated by Ca2+/calmodulin-mediated pathways and is enhanced in response to neuronal excitation. In addition to this fast regulation, we describe here a slower form of the regulation of H2S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator. Endogenous H2S in the mouse brain increases after birth, reaches a maximum level at 8 weeks and then decreases. Female brain contains less H2S than male brain at each age. A single administration of testosterone to female mice increases the endogenous H2S and SAM, which reach levels similar to those of male mice. In contrast, castration of male mice decreases the levels of testosterone, SAM and H2S in the brain. Administration of SAM once a day for 3 days increases the brain H2S without significantly changing the testosterone level. These observations suggest that testosterone can regulate the brain H2S level via changing the level of SAM.

A novel presenilin-binding protein (PBP) is specifically expressed in the brain, and its level in the soluble fraction of Alzheimer's disease (AD) brains is much less than that in the age-matched controls. Recently, several proteins, including presenilin (PS), have been found to form structures of aggregated proteins, called aggresomes, when the production of the proteins exceeds their rate of degradation by proteasomes. Based on these observations it has been proposed that the aggresome may represent one of the mechanisms forthe formation of cytoplasmic deposits which are linked to the pathogenesis of neurodegenerative disorders including AD. It is shown here that the overexpression of PBP or the suppression of proteasome activity in monkey kidney COS-7 cells leads to the accumulation of detergent-insoluble and multiubiquitinated PBP aggregates. PBP also forms aggregates in primary cultures of neurons in the presence of a proteasome inhibitors. PBP aggregates have the characteristics of aggresomes, including the localization to microtubule organization centers and the disruption of intermediate filaments. These observations suggest that the malfunctioning of the proteasome can cause the formation of PBP aggresomes, which may lead to AD.

Endogenous levels of sulfide in the brain have been measured in rats, humans and bovines in 1989 and 1990, suggesting that H(2)S may have a physiological function. We demonstrated in 1996 that cystathionine β-synthase can produce H(2)S in the brain and that H(2)S facilitates the induction of hippocampal long-term potentiation by enhancing the activity of NMDA receptors. The following year, we showed that another H(2)S-producing enzyme, cystathionine γ-lyase, is expressed in the thoracic aorta, portal vein and ileum and that H(2)S relaxes these tissues. We proposed that H(2)S may be a neuromodulator as well as a smooth muscle relaxant. In addition to a function as a signalling molecule, we demonstrated another function as a cytoprotectant in 2004. Hydrogen sulfide protects neurons from oxidative stress by reinstating the reduced glutathione levels. We recently demonstrated that a third H(2)S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST), is expressed in neurons and vascular endothelium. In addition to reinstating glutathione levels, H(2)S produced by 3MST, which is mainly localized to mitochondria, reduces reactive oxygen species generated in these organelles.

Approximately 50% of familial Alzheimer's disease (AD) cases are linked to the presenilin (PS) gene. This suggests that an altered function of mutated PSs accounts for a fundamental process leading to AD. Here we identify a new PS binding protein, PBP, which is highly expressed in cerebral cortex and hippocampus. immunohistochemical studies and cell fractionation analysis show that PBP redistributes from cytoplasm to membranes in the presence of PS. In addition, PBP is deficient in the soluble fraction of sporadic AD brains.

Single phase Bi2FeMnO6 films on (100) SrTiO3 substrate were fabricated using a pulsed laser deposition method through optimization of the preparation conditions. The magnetic moment is 0.30μB at 5 K in the magnetic field of 1 T, indicating that B site cations of Fe and Mn are disordered in the sample. The zero-field-cooling (ZFC) and field-cooling (FC) magnetization curves measured from 2 K to 400 K coincide at 360 K. This is consistent with the observation that hysteresis disappears at 360 K, revealing the antiferromagnetic transition at this temperature. A spin-glass-like behaviour was observed at low temperature (∼100 K) with a cusp of 25 K. Mn shows multiple valence states in the film. It is possibly because Mn2+ and Mn4+ could decrease the Jahn–Teller effect from Mn3+ in the film which results in less lattice distortion. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The gas permeation characteristics of poly(silamine) membrane, which consists of alternating 3,3-dimethyl-3-silapentane and N,N′-diethylethylenediamine units in the main chain, were investigated. Though poly(silamine) shows high flexibility (glass transition temperature of −88°C), the gas permeabilities were much lower than those of other rubbery polymers such as poly(dimethylsiloxane) and natural rubber. The activation energies of diffusion in poly(silamine) were much higher than that of natural rubber. On the basis of these results, we propose a model such that the interaction between the Si atom and gas molecules (O2 and N2) prevents the free diffusion of the gas molecule in the poly(silamine) membrane. © 1997 John Wiley & Sons, Ltd.

A novel aqueous chemical solution was developed as a precursor both for LiNbO3 powder and thin film. In this method, hydrogen peroxide aqueous solution (H2O2) reacts with niobium and lithium alkoxide ethanol solution to form metal peroxide aqueous solution. From this solution, crystalline LiNbO3 were synthesized at a temperature as low as 350°C. LiNbO3 thin films with well-developed grains were fabricated by spin-coating on silicon and sapphire substrates. In comparison with the alkoxide solution method, this peroxide solution method provides significant advantages, such as low weight loss in the sintering process and easy handling.

Optical absorption has been measured from 700 to 1300 nm for garnet single crystals by substituting Dy or Ga for Gd or Al of Dy 3 Ga 5 O 12 grown by the Czochralski method, and a suppression of unstable spiral-shape growth on Dy 3 Ga 5 O 12 by the substitution was discussed relating the absorption spectra. The total absorption in the single crystals at the wavelength corresponding to the radiation front Ir crucible was decreased relatively with the increase of Gd or Al content. The decrease of this absorption in the single crystals is one of the causes to suppress the unstable spiral-shape growth.

SPECIFIC AIMHydrogen sulfide (H2S), a well-known toxic gas, is found in relatively high concentrations in the brain. Although a neuromodulatory role of H2S has been demonstrated, little is known about its other biological functions. In the present study we determined that H2S protects primary cultures of neurons from death in a well-studied model of oxidative stress caused by glutamate, a process called oxidative glutamate toxicity, or oxytosis. We specifically examined the neuroprotective role of H2S and its mechanism.PRINCIPAL FINDINGS1. H2S protects neurons from oxidative stressBecause H2S, an endogenous reducing agent, is produced in response to oxidative stress in yeast, it is possible that H2S functions as an antioxidant. The effect of H2S on oxytosis was examined using primary cultures of neurons. Primary cultures of cortical immature neurons, which lack ionotropic glutamate receptors during their first few days in culture, were prepared from 17-day-old embryonic rat brains and cultured for 1 day. ...

Hydrogen sulfide (H2S) modifies hippocampal long-term potentiation (LTP) and functions as a neuromodulator. Here, we show that H2S increases intracellular Ca2+ and induces Ca2+ waves in primary cultures of astrocytes as well as hippocampal slices. H2S increases the influx of Ca2+ and to a lesser extent causes the release from intracellular Ca2+ stores. Ca2+ waves induced by neuronal excitation as well as responses to exogenously applied H2S are potently blocked by La3+ and Gd3+, inhibitors of Ca2+ channels. These observations suggest that H2S induces Ca2+ waves that propagate to neighboring astrocytes.

The response of cells of the megakaryocytic lineage to interleukin 6 (IL6), a cytokine with multiple biological activities, was studied by adding the factor to human bone marrow (BM) cultures. IL6 alone had no effect on megakaryocytic colony formation in methylcellulose; however, in the presence of maximally stimulating concentrations of IL 3, almost a twofold increment in colony formation was observed. Tritiated thymidine suicide studies of BM incubated for 2 h with growth factors showed that almost one-half of megakaryocytic progenitors (CFU-Mk) preincubated with IL3 or IL3 plus IL6 were in S phase, whereas BM incubated with IL6 alone was similar to control (approximately 24% of CFU-Mk in S phase). When greater than or equal to 1 ng/ml of IL6 was added to liquid suspension cultures of BM, the size of individual megakaryocytes was significantly augmented compared with that seen in control cultures. Moreover, the DNA content of megakaryocytes grown in the presence of IL6 was increased (modal ploidy 16N) compared with cultures grown with IL3 (modal ploidy 8N). To determine if the effect of IL6 could be direct rather than mediated via accessory BM cells, the factor was added to cultures of isolated single megakaryocytes. Seventy-one percent of cells increased in diameter in the presence of IL6, while only 27% increased in size in the absence of the factor. The data show that IL6 is a direct maturation factor for human megakaryocytes, promoting increments in size and ploidy of these cells.

Climbing fibre responses (c.f.r.s) evoked by white matter stimulation and the depolarizations induced by iontophoretically applied L-glutamate and L-aspartate were recorded intracellularly from the proximal dendrites of Purkinje cells in in vitro slice preparations of the guinea-pig cerebellum. Short pulses of L-glutamate and L-aspartate dose-dependently depolarized the Purkinje cell dendrite. Even small doses of these amino acids reduced the input resistance. The maximum decrease in input resistance induced by L-glutamate was 36% and that by L-aspartate was 38%. Intracellular injection of Cs+ allowed Purkinje cell dendrites to be depolarized to a range of -15 to +30 mV. The mean reversal potential for the c.f.r. (Ec) was found to be +10.2 mV (n = 4). The mean reversal potentials obtained for L-glutamate (Eg) and for L-aspartate (Ea) were +7.3 mV (n = 7) and +5.6 mV (n = 7) respectively. When external Na+ concentration was reduced, Ec, Ea and Eg were linearly and similarly shifted in the negative direction, indicating that all these reversal potentials are determined primarily by a Na+ conductance. The effects of the glutamate antagonists 2-amino-5-phosphonovaleric acid (APV), gamma-D-glutamylglycine (gamma-DGG), N-methyl-DL-aspartic acid (NMDLA) and glutamic acid diethylester (GDEE) were compared as to the responses to L-glutamate and L-aspartate and Ca2+-activated focal climbing fibre responses (c.f.c.f.r.s) in order to investigate the receptor type at the synapses formed by the climbing fibres with Purkinje cell dendrites. The order of antagonistic potency to the c.f.c.f.r. was : APV (mean percentage blockade = 99%) greater than gamma-DGG (87%) greater than NMDLA (71%) greater than GDEE (28%). The order of antagonistic potency to the response to L-aspartate was: gamma-DGG (69%) greater than APV (66%) greater than NMDLA (60%) greater than GDEE (31%), and that to the response to L-glutamate was: GDEE (63%) greater than NMDLA (22%) greater than gamma-GDD (15%) greater than APV (14%). APV was found to be the most effective anatagonist of the c.f.c.f.r. Its action was reversible, selective for L-aspartate-induced depolarization and had no effect on the responses to L-glutamate. NMDLA, which has no activity as an agonist, was a greater suppressant of the responses to L-aspartate than those to L-glutamate. These electrophysiological and pharmacological findings suggest that the receptor for the transmitter at the synapses formed by climbing fibres with Purkinje cell dendrites is of the L-aspartate-preferring type, and are thus consistent with the bio-and histochemical findings that L-aspartate may be the endogenous transmitter at this synapse.