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1.
Redox Biol ; 53: 102345, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35653932

RESUMO

Heterotrophic bacteria and human mitochondria often use sulfide: quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO) to oxidize sulfide to sulfite and thiosulfate. Bioinformatic analysis showed that the genes encoding RHOD domains were widely presented in annotated sqr-pdo operons and grouped into three types: fused with an SQR domain, fused with a PDO domain, and dissociated proteins. Biochemical evidence suggests that RHODs facilitate the formation of thiosulfate and promote the reaction between inorganic polysulfide and glutathione to produce glutathione polysulfide. However, the physiological roles of RHODs during sulfide oxidation by SQR and PDO could only be tested in an RHOD-free host. To test this, 8 genes encoding RHOD domains in Escherichia coli MG1655 were deleted to produce E. coli RHOD-8K. The sqrCp and pdoCp genes from Cupriavidus pinatubonensis JMP134 were cloned into E. coli RHOD-8K. SQRCp contains a fused RHOD domain at the N-terminus. When the fused RHOD domain of SQRCp was inactivated, the cells oxidized sulfide into increased thiosulfate with the accumulation of cellular sulfane sulfur in comparison with cells containing the intact sqrCp and pdoCp. The complementation of dissociated DUF442 minimized the accumulation of cellular sulfane sulfur and reduced the production of thiosulfate. Further analysis showed that the fused DUF442 domain modulated the activity of SQRCp and prevented it from directly passing the produced sulfane sulfur to GSH. Whereas, the dissociated DUF442 enhanced the PDOCp activity by several folds. Both DUF442 forms minimized the accumulation of cellular sulfane sulfur, which spontaneously reacted with GSH to produce GSSG, causing disulfide stress during sulfide oxidation. Thus, RHODs may play multiple roles during sulfide oxidation.


Assuntos
Sulfeto de Hidrogênio , Quinona Redutases , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Dissulfetos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Glutationa/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Quinona Redutases/química , Quinona Redutases/genética , Quinona Redutases/metabolismo , Sulfetos/metabolismo , Enxofre/metabolismo , Tiossulfato Sulfurtransferase/genética , Tiossulfato Sulfurtransferase/metabolismo , Tiossulfatos/metabolismo
2.
BMC Plant Biol ; 22(1): 296, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710355

RESUMO

BACKGROUND: Sediment is crucial for the unique marine angiosperm seagrass growth and successful restoration. Sediment modification induced by eutrophication also exacerbates seagrass decline and reduces plantation and transplantation survival rates. However, we lack information regarding the influence of sediment on seagrass photosynthesis and the metabolics, especially regarding the key secondary metabolic flavone. Meanwhile, sulfation of flavonoids in seagrass may mitigate sulfide intrusion, but limited evidence is available. RESULTS: We cultured the seagrass Thalassia hemprichii under controlled laboratory conditions in three sediment types by combining different ratios of in-situ eutrophic sediment and coarse beach sand. We examined the effects of beach sand mixed with natural eutrophic sediments on seagrass using photobiology, metabolomics and isotope labelling approaches. Seagrasses grown in eutrophic sediments mixed with beach sand exhibited significantly higher photosynthetic activity, with a larger relative maximum electron transport rate and minimum saturating irradiance. Simultaneously, considerably greater belowground amino acid and flavonoid concentrations were observed to counteract anoxic stress in eutrophic sediments without mixed beach sand. This led to more positive belowground stable sulfur isotope ratios in eutrophic sediments with a lower Eh. CONCLUSIONS: These results indicated that coarse beach sand indirectly enhanced photosynthesis in T. hemprichii by reducing sulfide intrusion with lower amino acid and flavonoid concentrations. This could explain why T. hemprichii often grows better on coarse sand substrates. Therefore, it is imperative to consider adding beach sand to sediments to improve the environmental conditions for seagrass and restore seagrass in eutrophic ecosystems.


Assuntos
Hydrocharitaceae , Aminoácidos/metabolismo , Baías , Suplementos Nutricionais , Ecossistema , Flavonoides/metabolismo , Hydrocharitaceae/metabolismo , Areia , Sulfetos/metabolismo
3.
STAR Protoc ; 3(2): 101424, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35634358

RESUMO

Hydrogen sulfide (H2S) and downstream reactive sulfur species (RSS), including organic persulfides, protect bacterial cells against diverse oxidative stressors. Specialized dithiol-based transcriptional repressors sense persulfides directly to control cellular H2S/RSS and avoid toxicity. Here, we present a protocol to quantify the kinetics of chemical reactivity of cysteines in two bacterial persulfide sensors toward cysteine persulfide and glutathione persulfide, with a LC-ESI-MS analysis that results in a kinetic model. This protocol has potential applications to other cysteine-containing proteins and oxidants. For complete details on the use and execution of this protocol, please refer to Fakhoury et al. (2021) and Capdevila et al. (2021).


Assuntos
Sulfeto de Hidrogênio , Sulfetos , Cromatografia Líquida , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Sulfetos/metabolismo
4.
Bioresour Technol ; 354: 127186, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35439563

RESUMO

The role of hydraulic retention time (HRT) on S0 production was assessed through metagenomics analyses. Considering comprehensive performance for the tested HRTs (0.25-13.33 h), the optimal HRT was 1 h, while respective sulfide and nitrite loading rate could reach 6.84 kg S/(m3·d) and 1.95 kg N/(m3·d), and total S0 yield was 0.36 kg S/(kg (VSS)·d). Bacterial community richness decreased along the shortening of HRT. Microbacterium, Sulfurimonas, Sulfurovum, Paracoccus and Thauera were highly abundant bacteria. During sulfur metabolism, high expression of sqr gene was the main reason of maintaining high desulfurization load, while lacking soxB caused the continuous increase of S0. Regarding nitrogen metabolism, the rapid decrease of nitrite transporter prevented nitrite to enter in cells, which caused a rapid decrease of nitrite removal under extreme HRT. Adjusting HRT is an effective way to enhance S0 production for the application of the simultaneous sulfide and nitrite removal process.


Assuntos
Microbiota , Nitritos , Bactérias/genética , Bactérias/metabolismo , Reatores Biológicos , Desnitrificação , Redes e Vias Metabólicas , Metagenômica , Nitritos/metabolismo , Nitrogênio/metabolismo , Sulfetos/metabolismo
5.
Ecotoxicol Environ Saf ; 236: 113479, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35366561

RESUMO

Effects of iron and sulfur redox states in the soil caused by different growth seasons on Cd uptake by rice remain unclear. In this study, three early rice cultivars and three late rice cultivars were cultivated in a double-cropping system in Cd-contaminated paddy fields. The total Cd accumulation of early rice cultivars was 20.5-51.1 µg plant-1, and the Cd concentration in grains was 0.19-0.73 mg kg-1, significantly lower than those of late rice cultivars by 8-15 times and 3-9 times, respectively. The filling and mature stages were identified as the most crucial stages of Cd uptake by both early and late rice cultivars. The growth season of early rice cultivars was characterized by more abundant rainfall and lower soil Eh than that for late rice cultivars. Therefore, the abundances of Fe-reducing bacteria (FeRB, 36.9-39%) and S-reducing bacteria (SRB, 1.77-2.79%) were higher during the filling and mature stages of early rice. They primarily belonged to the Clostridium, Geobacter, and Desulfuromonadales genera. Stimulation of FeRB and SRB activity promoted Fe(III) and S reduction and increased the content of Fe2+ and S2- in rhizosphere soil. This promoted the binding of Cd to amorphous Fe oxides and sulfides or Fe sulfides, thereby decreasing the available Cd content. Moreover, the Cd in the iron plaque (IP) and Cd transfer from IP to roots were lower in early rice. These findings suggest that maintaining high moisture content in the soil during the filling and mature stages, especially for late rice cultivars, could efficiently reduce Cd uptake by rice planted in contaminated soil.


Assuntos
Oryza , Poluentes do Solo , Cádmio/metabolismo , Ferro/química , Oryza/metabolismo , Estações do Ano , Solo/química , Poluentes do Solo/análise , Sulfetos/metabolismo , Enxofre/metabolismo
6.
Mar Drugs ; 20(3)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35323515

RESUMO

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.


Assuntos
Anti-Inflamatórios , Aspergillus/química , Produtos Biológicos , Peptídeos Cíclicos , Sulfetos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Organismos Aquáticos , Aspergillus/metabolismo , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitrogênio/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/metabolismo , Pirrolidinonas/química , Pirrolidinonas/isolamento & purificação , Pirrolidinonas/metabolismo , Células RAW 264.7 , Metabolismo Secundário , Sulfetos/química , Sulfetos/isolamento & purificação , Sulfetos/metabolismo
7.
Biomolecules ; 12(3)2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35327553

RESUMO

The present article will not attempt to deal with sulfide per se as a signaling molecule but will aim to examine the consequences of sulfide oxidation by mitochondrial sulfide quinone reductase in mammalian cells. This oxidation appears first as a priority to avoid self-poisoning by endogenous sulfide and second to occur with the lowest ATP/O2 ratio when compared to other mitochondrial substrates. This is explained by the injection of electrons in the respiratory chain after complex I (as for succinate) and by a sulfur oxidation step implying a dioxygenase that consumes oxygen but does not contribute to mitochondrial bioenergetics. Both contribute to increase cellular oxygen consumption if sulfide is provided below its toxic level (low µM). Accordingly, if oxygen supply or respiratory chain activity becomes a limiting factor, small variations in sulfide release impact the cellular ATP/ADP ratio, a major metabolic sensor.


Assuntos
Mitocôndrias , Oxigênio , Trifosfato de Adenosina/metabolismo , Animais , Transporte de Elétrons , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Oxirredução , Oxigênio/metabolismo , Consumo de Oxigênio , Sulfetos/metabolismo
8.
Bioresour Technol ; 351: 127026, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35314309

RESUMO

Dissimilatory sulfate reduction (DSR) in cake layer of full-scale anaerobic dynamic membrane bioreactor for treating hotel laundry wastewater was studied. Change (Δ) of sulfate concentration (ΔSO42-) was positively correlated to dynamic cake layer (DCL) development, while ΔS2- was negatively correlated. ΔSO32- and ΔSorganic sulfur remained around 1.5-2.5 and 1.2-2.3 mg-S/L, respectively. Thus, DSR was the predominant sulfate reduction process in DCL. 33 binned genomes from DCL microbiome samples possessed one or more DSR functional genes. But only four binned genomes possess all functional genes, and thus can achieve complete DSR. However, no significant variations of these DSR bacteria was obseared during DCL development. Metagenomic analysis predicted that sulfate reduction in DCL was mainly carried out by collaborations between bacteria with incomplete DSR pathways. Among which, sulfite â†’ sulfide by dissimilatory-sulfite-reductase expression bacteria was the key process. Overall results suggested that controlling dissimilatory-sulfite-reductase activities could prevent sulfide buildup in the effluent.


Assuntos
Reatores Biológicos , Águas Residuárias , Anaerobiose , Bactérias/genética , Bactérias/metabolismo , Oxirredução , Oxirredutases/metabolismo , Sulfatos/metabolismo , Sulfetos/metabolismo , Sulfitos
9.
Sci Total Environ ; 828: 154537, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35292324

RESUMO

Anthropogenic input of sulfate (SO42-) in reservoirs may enhance bacterial sulfate reduction (BSR) under seasonally hypoxic conditions in the water column. However, factors that control BSR and its coupling to organic carbon (OC) mineralization in seasonally hypoxic reservoirs remain unclear. The present study elucidates the coupling processes by analyzing the concentrations and isotopic composition of dissolved inorganic carbon (DIC) and sulfur (SO42-, sulfide) species, and the microbial community in water of the Aha reservoir, SW China, which has high SO42- concentration due to the inputs from acid mine drainage about twenty years ago. The water column at two sites in July and October revealed significant thermal stratification. In the hypoxic bottom water, the δ13C-DIC decreased while the δ34S-SO42- increased, implying organic carbon mineralization due to BSR. The magnitude of S isotope fractionation (Δ34S, obtained from δ34Ssulfate-δ34Ssulfide) during the process of BSR fell in the range of 3.4‰ to 27.0‰ in July and 21.6‰ to 31.8‰ in October, suggesting a change in the community of sulfate-reducing bacteria (SRB). The relatively low water column stability in October compared to that in July weakened the difference of water chemistry and ultimately affected the SRB diversity. The production of DIC (ΔDIC) scaled a strong positive relationship with the Δ34S in July (p < 0.01), indicating that high OC availability favored the survival of incomplete oxidizers of SRB. However, in October, Δ13C-DIC was correlated with the Δ34S in the bottom hypoxic water (p < 0.01), implying that newly degraded OC depleted in 13C could favor the dominance of complete oxidizers of SRB which caused greater S isotope fractionation. Moreover, the sulfide supplied by BSR might stimulate the reductive dissolution of Fe and Mn oxides (Fe(O)OH and MnO2). The present study helps to understand the coupling of C and S in seasonally hypoxic reservoirs characterized by high SO42- concentration.


Assuntos
Carbono , Sulfatos , Bactérias/metabolismo , Carbono/metabolismo , Isótopos de Carbono/análise , China , Dacarbazina/metabolismo , Monitoramento Ambiental , Isótopos , Compostos de Manganês , Óxidos , Sulfatos/análise , Sulfetos/metabolismo , Enxofre/metabolismo , Isótopos de Enxofre/análise , Óxidos de Enxofre/metabolismo , Água/metabolismo
10.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269857

RESUMO

The intertidal zone is a transitional area of the land-sea continuum, in which physical and chemical properties vary during the tidal cycle and highly toxic sulfides are rich in sediments due to the dynamic regimes. As a typical species thriving in this habitat, Urechis unicinctus presents strong sulfide tolerance and is expected to be a model species for sulfide stress research. Heat shock proteins (HSPs) consist of a large group of highly conserved molecular chaperones, which play important roles in stress responses. In this study, we systematically analyzed the composition and expression of HSPs in U. unicinctus. A total of eighty-six HSP genes from seven families were identified, in which two families, including sHSP and HSP70, showed moderate expansion, and this variation may be related to the benthic habitat of the intertidal zone. Furthermore, expression analysis revealed that almost all the HSP genes in U. unicinctus were significantly induced under sulfide stress, suggesting that they may be involved in sulfide stress response. Weighted gene co-expression network analysis (WGCNA) showed that 12 HSPs, including 5 sHSP and 4 HSP70 family genes, were highly correlated with the sulfide stress response which was distributed in steelblue and green modules. Our data indicate that HSPs, especially sHSP and HSP70 families, may play significant roles in response to sulfide stress in U. unicinctus. This systematic analysis provides valuable information for further understanding of the function of the HSP gene family for sulfide adaptation in U. unicinctus and contributes a better understanding of the species adaptation strategies of marine benthos in the intertidal zone.


Assuntos
Anelídeos , Poliquetos , Animais , Anelídeos/genética , Estudo de Associação Genômica Ampla , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Poliquetos/genética , Poliquetos/metabolismo , Sulfetos/metabolismo
11.
PLoS One ; 17(2): e0254910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35213532

RESUMO

The mutualism between the thioautotrophic bacterial ectosymbiont Candidatus Thiobius zoothamnicola and the giant ciliate Zoothamnium niveum thrives in a variety of shallow-water marine environments with highly fluctuating sulfide emissions. To persist over time, both partners must reproduce and ensure the transmission of symbionts before the sulfide stops, which enables carbon fixation of the symbiont and nourishment of the host. We experimentally investigated the response of this mutualism to depletion of sulfide. We found that colonies released some initially present but also newly produced macrozooids until death, but in fewer numbers than when exposed to sulfide. The symbionts on the colonies proliferated less without sulfide, and became larger and more rod-shaped than symbionts from freshly collected colonies that were exposed to sulfide and oxygen. The symbiotic monolayer was severely disturbed by growth of other microbes and loss of symbionts. We conclude that the response of both partners to the termination of sulfide emission was remarkably quick. The development and the release of swarmers continued until host died and thus this behavior contributed to the continuation of the association.


Assuntos
Cilióforos/genética , Rhizobiaceae/genética , Sulfetos/metabolismo , Simbiose/genética , Animais , Organismos Aquáticos/genética , Organismos Aquáticos/fisiologia , Bactérias/genética , Ciclo do Carbono/genética , Cilióforos/fisiologia , Filogenia , Rhizobiaceae/fisiologia
12.
ISME J ; 16(6): 1523-1533, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35124702

RESUMO

The reduction of manganese oxide with sulfide in aquatic redox-stratified systems was previously considered to be mainly chemical, but recent isolation of the Black Sea isolate Candidatus Sulfurimonas marisnigri strain SoZ1 suggests an important role for biological catalyzation. Here we provide evidence from laboratory experiments, field data, and modeling that the latter process has a strong impact on redox zonation in the Black Sea. High relative abundances of Sulfurimonas spp. across the redoxcline in the central western gyre of the Black Sea coincided with the high-level expression of both the sulfide:quinone oxidoreductase gene (sqr, up to 93% expressed by Sulfurimonas spp.) and other sulfur oxidation genes. The cell-specific rate of manganese-coupled sulfide oxidation by Ca. S. marisnigri SoZ1 determined experimentally was combined with the in situ abundance of Sulfurimonas spp. in a one-dimensional numerical model to calculate the vertical sulfide distribution. Abiotic sulfide oxidation was too slow to counterbalance the sulfide flux from euxinic water. We conclude that microbially catalyzed Mn-dependent sulfide oxidation influences the element cycles of Mn, S, C, and N and therefore the prevalence of other functional groups of prokaryotes (e.g., anammox bacteria) in a sulfide-free, anoxic redox zone.


Assuntos
Manganês , Água , Mar Negro , Oxirredução , Água do Mar/microbiologia , Sulfetos/metabolismo
13.
Free Radic Biol Med ; 182: 119-131, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35202787

RESUMO

In the canonical pathway for mitochondrial H2S oxidation electrons are transferred from sulfide:quinone oxidoreductase (SQR) to complex III via ubiquinone (CoQ10). We previously observed that a number of quinones directly oxidize H2S and we hypothesize that CoQ10 may have similar properties. Here we examine H2S oxidation by CoQ10 and more hydrophilic, truncated forms, CoQ1 and CoQ0, in buffer using H2S and polysulfide fluorophores (AzMC and SSP4), silver nanoparticles to measure thiosulfate (H2S2O3), mass spectrometry to identify polysulfides and O2-sensitive optodes to measure O2 consumption. We show that all three quinones concentration-dependently catalyze the oxidization of H2S to polysulfides and thiosulfate in buffer with the potency CoQ0>CoQ1>CoQ10 and that CoQ0 specifically oxidizes H2S to per-polysulfides, H2S2,3,4. These reactions consume and require oxygen and are augmented by addition of SOD suggesting that the quinones, not superoxide, oxidize H2S. Related quinones, MitoQ, menadione and idebenone, oxidize H2S in similar reactions. Exogenous CoQ0 decreases cellular H2S and increases polysulfides and thiosulfate production and this is also O2-dependent, suggesting that the quinone has similar effects on sulfur metabolism in cells. Collectively, these results suggest an additional endogenous mechanism for H2S metabolism and a potential therapeutic approach in H2S-related metabolic disorders.


Assuntos
Sulfeto de Hidrogênio , Nanopartículas Metálicas , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Quinonas , Prata , Sulfetos/metabolismo , Tiossulfatos , Ubiquinona/metabolismo
14.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35163277

RESUMO

Hydrogen sulfide (H2S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of H2S and polysulfides on adipose tissue lipolysis. H2S and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of Na2S and Na2S4, the H2S and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. Na2S but not Na2S4 increased plasma NEFA and glycerol in a time- and dose-dependent manner. Na2S increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of Na2S on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of Na2S on lipolysis was not abolished by propranolol, suggesting no involvement of ß-adrenergic receptors. In addition, Na2S had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater H2S production in the adipose tissue. In conclusion, H2S stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.


Assuntos
Tecido Adiposo/metabolismo , Sulfeto de Hidrogênio/metabolismo , Lipólise/fisiologia , Tecido Adiposo/efeitos dos fármacos , Animais , GMP Cíclico/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Lipólise/efeitos dos fármacos , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Obesidade/metabolismo , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/metabolismo , Sulfetos/metabolismo
15.
J Biol Chem ; 298(3): 101661, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35101450

RESUMO

High levels of H2S produced by gut microbiota can block oxygen utilization by inhibiting mitochondrial complex IV. Kumar et al. have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport. The reverse activity of mitochondrial complex II (succinate-quinone oxidoreductase, i.e., fumarate reduction) generates oxidized coenzyme Q, which is then reduced by the mitochondrial sulfide quinone oxidoreductase to oxidize H2S. This newly identified redox circuitry points to the importance of complex II reversal in mitochondria during periods of hypoxia and cellular stress.


Assuntos
Complexo II de Transporte de Elétrons , Sulfeto de Hidrogênio , Sulfetos , Transporte de Elétrons , Complexo II de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Sulfetos/metabolismo
16.
Mol Med Rep ; 25(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35059738

RESUMO

The present study explored the protective effect of exogenous hydrogen sulfide (H2S) on lipopolysaccharide (LPS)­induced acute kidney injury (AKI) and the underlying mechanisms. To establish an AKI injury mouse model, LPS (10 mg/kg) was intraperitoneally injected into mice pretreated with 0.8 mg/kg sodium hydrosulfide hydrate (NaHS), an H2S donor. The mouse survival rate and the degree of kidney injury were examined. To construct a cell damage model, HK­2 cells were pretreated with different concentrations (0.1, 0.3 and 0.5 mM) of NaHS, and then the cells were stimulated with LPS (1 µg/ml). The cell viability, autophagy, apoptosis levels and the release of inflammatory factors were examined in mouse kidney tissue and HK­2 renal tubular epithelial cells. It was found that pretreatment with NaHS significantly improved the survival rate of septic AKI mice, and reduced the renal damage, release of inflammatory factors and apoptosis. In HK­2 cells, NaHS protected cells from LPS caused damage via promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. In order to clarify the relationship between autophagy and apoptosis and inflammatory factors, this study used 3­methyladenine (3­MA) to inhibit autophagy. The results revealed that 3­MA eliminated the protective effect of NaHS in HK­2 cells and AKI mice. Overall, NaHS can protect from LPS­induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors.


Assuntos
Injúria Renal Aguda/prevenção & controle , Autofagia/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Rim/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sulfeto de Hidrogênio/metabolismo , Rim/patologia , Rim/ultraestrutura , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Sulfetos/metabolismo , Sulfetos/farmacologia
17.
Fundam Clin Pharmacol ; 36(3): 536-552, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34984731

RESUMO

Phosphonium compounds offer an attractive branch of research that chemists and biologists apply for producing many novel drugs for various applications, and its polymeric ingredients are composed of quaternary ammonium and phosphonium salts. The reactions of isothiocyanate with phosphinimine bestow thiaziridine, carbamate, and thiourea derivatives. Moreover, isothiocyanate reacts with tris (dimethylamino) phosphine leading to the formation of sulfidomethyl phosphonium. Lawesson's and Japanese reagents have potential to react with isothiocyanates to generate dithiaphosphetane sulfides. Treatment of isocyanate with Lawesson' s or Japanese reagents under reflux conditions affords thiaphosphetidinone sulfide, but when applied at room temperature, the dithiaphosphetane sulfide was isolated. Ehrlich ascites carcinoma (EAC) mice model was used to investigate potential anticancer properties of the novel phosphonium and thiophosphate derivatives. Synthesized compounds (100 mg/kg b.w.) were administered orally to the EAC-bearing mice for about 2 weeks. Compounds' antineoplastic activity was determined by the evaluation of volume, viability, and inhibition percent of EAC cells. In addition, DNA fragmentation percent was assessed. The expression of apoptotic marker genes (Bax, Bcl2, Caspase 3) and encoding proinflammatory cytokines (TNF-α) and pro-apoptotic protein (p53) were inspected by real time-quantitative polymerase chain reaction (RT-qPCR). The overall conclusion was based on the findings that treatment with synthesized compounds leads to decrease in tumor volume, increase in tissue DNA fragmentation, downregulation of Bcl2 gene, and upregulation of Bax, caspase3, and p53 markers, along with decrease in TNF-α level in liver tissues. These findings suggest that the anticancer mechanism of these compounds is based on the programmed cell death (Apoptosis).


Assuntos
Antineoplásicos , Carcinoma de Ehrlich , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Ascite/tratamento farmacológico , Ascite/patologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfetos/metabolismo , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2/metabolismo
18.
Drug Metab Dispos ; 50(4): 361-373, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35086846

RESUMO

CPI-613, an inhibitor of pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) enzymes, is currently in development for the treatment of pancreatic cancer, acute myeloid leukemia, and other cancers. CPI-613 is an analog of lipoic acid, an essential cofactor for both PDH and KGDH. Metabolism and mass balance studies were conducted in rats after intravenous administration of [14C]-CPI-613. CPI-613 was eliminated via oxidative metabolism followed by excretion of the metabolites in feces (59%) and urine (22%). ß-Oxidation was the major pathway of elimination for CPI-613. The most abundant circulating components in rat plasma were those derived from ß-oxidation. In human hepatocytes, CPI-613 mainly underwent ß-oxidation (M1), sulfur oxidation (M2), and glucuronidation (M3). The Michaelis-Menten kinetics (Vmax and Km) of the metabolism of CPI-613 to these three metabolites predicted the fraction metabolized leading to the formation of M1, M2, and M3 to be 38%, 6%, and 56%, respectively. In humans, after intravenous administration of CPI-613, major circulating species in plasma were the parent and the ß-oxidation derived products. Thus, CPI-613 metabolites profiles in rat and human plasma were qualitatively similar. ß-Oxidation characteristics and excretion patterns of CPI-613 are discussed in comparison with those reported for its endogenous counterpart, lipoic acid. SIGNIFICANCE STATEMENT: This work highlights the clearance mechanism of CPI-613 via ß-oxidation, species differences in their ability to carry out ß-oxidation, and subsequent elimination routes. Structural limitations for completion of terminal cycle of ß-oxidation is discussed against the backdrop of its endogenous counterpart lipoic acid.


Assuntos
Caprilatos , Neoplasias , Animais , Caprilatos/metabolismo , Hepatócitos/metabolismo , Humanos , Neoplasias/metabolismo , Ratos , Sulfetos/metabolismo
19.
Appl Environ Microbiol ; 88(3): e0194121, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878813

RESUMO

Sulfur-oxidizing bacteria can oxidize hydrogen sulfide (H2S) to produce sulfur globules. Although the process is common, the pathway is unclear. In recombinant Escherichia coli and wild-type Corynebacterium vitaeruminis DSM 20294 with sulfide:quinone oxidoreductase (SQR) but no enzymes to oxidize zero valence sulfur, SQR oxidized H2S into short-chain inorganic polysulfide (H2Sn, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), which reacted with each other to form long-chain GSnH (n ≥ 2) and H2Sn before producing octasulfur (S8), the main component of elemental sulfur. GSnH also reacted with glutathione (GSH) to form GSnG (n ≥ 2) and H2S; H2S was again oxidized by SQR. After GSH was depleted, SQR simply oxidized H2S to H2Sn, which spontaneously generated S8. S8 aggregated into sulfur globules in the cytoplasm. The results highlight the process of sulfide oxidation to S8 globules in the bacterial cytoplasm and demonstrate the potential of using heterotrophic bacteria with SQR to convert toxic H2S into relatively benign S8 globules. IMPORTANCE Our results provide evidence of H2S oxidation producing octasulfur globules via sulfide:quinone oxidoreductase (SQR) catalysis and spontaneous reactions in the bacterial cytoplasm. Since the process is an important event in geochemical cycling, a better understanding facilitates further studies and provides theoretical support for using heterotrophic bacteria with SQR to oxidize toxic H2S into sulfur globules for recovery.


Assuntos
Sulfeto de Hidrogênio , Quinona Redutases , Bactérias Aeróbias/metabolismo , Citoplasma/metabolismo , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Quinona Redutases/metabolismo , Sulfetos/metabolismo
20.
Appl Environ Microbiol ; 88(2): e0180621, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-34788071

RESUMO

Dimethylsulfoniopropionate (DMSP) is one of the most abundant organic sulfur compounds in the oceans, which is mainly degraded by bacteria through two pathways, a cleavage pathway and a demethylation pathway. Its volatile catabolites dimethyl sulfide (DMS) and methanethiol (MT) in these pathways play important roles in the global sulfur cycle and have potential influences on the global climate. Intense DMS/DMSP cycling occurs in the Arctic. However, little is known about the diversity of cultivable DMSP-catabolizing bacteria in the Arctic and how they catabolize DMSP. Here, we screened DMSP-catabolizing bacteria from Arctic samples and found that bacteria of four genera (Psychrobacter, Pseudoalteromonas, Alteromonas, and Vibrio) could grow with DMSP as the sole carbon source, among which Psychrobacter and Pseudoalteromonas are predominant. Four representative strains (Psychrobacter sp. K31L, Pseudoalteromonas sp. K222D, Alteromonas sp. K632G, and Vibrio sp. G41H) from different genera were selected to probe their DMSP catabolic pathways. All these strains produce DMS and MT simultaneously during their growth on DMSP, indicating that all strains likely possess the two DMSP catabolic pathways. On the basis of genomic and biochemical analyses, the DMSP catabolic pathways in these strains were proposed. Bioinformatic analysis indicated that most Psychrobacter and Vibrio bacteria have the potential to catabolize DMSP via the demethylation pathway and that only a small portion of Psychrobacter strains may catabolize DMSP via the cleavage pathway. This study provides novel insights into DMSP catabolism in marine bacteria. IMPORTANCE Dimethylsulfoniopropionate (DMSP) is abundant in the oceans. The catabolism of DMSP is an important step of the global sulfur cycle. Although Gammaproteobacteria are widespread in the oceans, the contribution of Gammaproteobacteria in global DMSP catabolism is not fully understood. Here, we found that bacteria of four genera belonging to Gammaproteobacteria (Psychrobacter, Pseudoalteromonas, Alteromonas and Vibrio), which were isolated from Arctic samples, were able to grow on DMSP. The DMSP catabolic pathways of representative strains were proposed. Bioinformatic analysis indicates that most Psychrobacter and Vibrio bacteria have the potential to catabolize DMSP via the demethylation pathway and that only a small portion of Psychrobacter strains may catabolize DMSP via the cleavage pathway. Our results suggest that novel DMSP dethiomethylases/demethylases may exist in Pseudoalteromonas, Alteromonas, and Vibrio and that Gammaproteobacteria may be important participants in the marine environment, especially in polar DMSP cycling.


Assuntos
Compostos de Sulfônio , Bactérias , Liases de Carbono-Enxofre/genética , Humanos , Sulfetos/metabolismo , Compostos de Sulfônio/metabolismo , Enxofre/metabolismo
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