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1.
BMC Genomics ; 20(1): 770, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646963

RESUMO

BACKGROUND: Host genotype plays a crucial role in microbial composition of laying hens, which may lead to dissimilar odor gas production. The objective of this study was to investigate the relationship among layer breed, microbial structure and odor production. RESULTS: Thirty Hy-Line Gray and thirty Lohmann Pink laying hens were used in this study to determine the impact of cecal microbial structure on odor production of laying hens. The hens were managed under the same husbandry and dietary regimes. Results of in vivo experiments showed a lower hydrogen sulfide (H2S) production from Hy-Line hens and a lower concentration of soluble sulfide (S2-) but a higher concentration of butyrate in the cecal content of the Hy-Line hens compared to Lohmann Pink hens (P < 0.05), which was consistent with the in vitro experiments (P < 0.05). However, ammonia (NH3) production was not different between genotypes (P > 0.05). Significant microbial structural differences existed between the two breed groups. The relative abundance of some butyrate producers (including Butyricicoccus, Butyricimonas and Roseburia) and sulfate-reducing bacteria (including Mailhella and Lawsonia) were found to be significantly correlated with odor production and were shown to be different in the 16S rRNA and PCR data between two breed groups. Furthermore, some bacterial metabolism pathways associated with energy extraction and carbohydrate utilization (oxidative phosphorylation, pyruvate metabolism, energy metabolism, two component system and secretion system) were overrepresented in the Hy-Line hens, while several amino acid metabolism-associated pathways (amino acid related enzymes, arginine and proline metabolism, and alanine-aspartate and glutamate metabolism) were more prevalent in the Lohmann hens. CONCLUSION: The results of this study suggest that genotype of laying hens influence cecal microbiota, which in turn modulates their odor production. Our study provides references for breeding and enteric manipulation for defined microbiota to reduce odor gas emission.


Assuntos
Bactérias/classificação , Ceco/microbiologia , Galinhas/microbiologia , Microbioma Gastrointestinal , Sulfeto de Hidrogênio/metabolismo , Animais , Bactérias/metabolismo , Butiratos , Feminino , Odorantes , RNA Ribossômico 16S/genética
2.
Nihon Yakurigaku Zasshi ; 154(3): 128-132, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527362

RESUMO

Hydrogen sulfide (H2S), an endogenous gasotransmitter, is generated from L-cysteine by 3 distinct enzymes including cystathionine-γ-lyase (CSE), and targets multiple molecules, thereby playing various roles in health and disease. H2S triggers or accelerates somatic pain and visceral nociceptive signals in the pancreas, colon and bladder by enhancing the activity of Cav3.2 T-type calcium channels. H2S also activates TRPA1, which participates in H2S-induced somatic pain signaling. However, Cav3.2 predominantly mediates colonic nociception by H2S, because genetic deletion of TRPA1 does not reduce H2S-induced colonic pain. The functional upregulation of the CSE/H2S/Cav3.2 system is involved in neuropathic pain and visceral pain accompanying pancreatitis and cystitis. Cav3.2 also appears to participate in irritable bowel syndrome (IBS), although the role of endogenous H2S generation by CSE in IBS is still open to question. In this review, we describe how H2S regulates pain signals, particularly by interacting with Cav3.2.


Assuntos
Canais de Cálcio Tipo T/metabolismo , Sulfeto de Hidrogênio/metabolismo , Neuralgia , Dor Visceral , Cistationina gama-Liase/metabolismo , Humanos , Síndrome do Intestino Irritável
3.
Nihon Yakurigaku Zasshi ; 154(3): 133-137, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527363

RESUMO

Hydrogen sulfide (H2S) has been focused as a biological mediator, which modulates signal transduction and protects cells and tissues from oxidative stress. H2S is also expected as a neuroprotectant because it has a neuroprotective activity. Endogenous H2S is mainly generated from L-cysteine. However, it is difficult to use L-cysteine as a neuroprotectant because of its neurotoxicity. In 2013, a novel biogenesis pathway of H2S from D-cysteine has been identified. In this pathway, D-amino acid oxidase (DAO) converts D-cysteine to 3-mercaptopyruvate (3MP), followed by the generation of H2S from 3MP by 3-mercaptopyrvate sulfurtransferase. DAO is especially abundant in cerebellum among various brain regions and mediates efficient generation of H2S from D-cysteine in the cerebellar tissues. In addition, D-cysteine has more potent neuroprotective activity in cerebellar primary neurons than L-cysteine. Cerebella Purkinje cells (PCs) are characterized by the highly-branched dendrites and are important for cerebellar functions. The dendritic shrinkage and degeneration of PCs are frequently observed in patients and model mice of cerebellar ataxias. We revealed that D-cysteine enhanced dendritic development of primary cultured PCs, but L-cysteine impaired the dendritic development. This effect of D-cysteine was inhibited by DAO inhibitors and reproduced by 3MP and a H2S donor, suggesting that this enhancement of dendritic development is caused by the production of H2S from D-cysteine. Taken together, D-cysteine would be available as a neuroprotectant against cerebellar ataxias, which are accompanied with dendritic shrinkage of cerebellar PCs.


Assuntos
Cisteína/metabolismo , Sulfeto de Hidrogênio/metabolismo , Neurônios/citologia , Fármacos Neuroprotetores/metabolismo , Animais , Células Cultivadas , D-Aminoácido Oxidase/antagonistas & inibidores , D-Aminoácido Oxidase/metabolismo , Humanos , Camundongos , Neurogênese , Estresse Oxidativo , Células de Purkinje/citologia
4.
Chem Commun (Camb) ; 55(68): 10142-10145, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31389424

RESUMO

Hydrogen sulfide, an endogenous signalling molecule, is central to several pathophysiological processes in mammalian systems. It scavenges reactive oxygen species and is known to ameliorate dopaminergic neuronal degeneration in neurotoxin-induced Parkinson's disease models. The rapid volatilization of H2S from spontaneously releasing sulfide salts being a challenge, we describe peptide conjugates which exhibit tris(2-carboxyethyl)phosphine mediated "slow and sustained" H2S release. These conjugates reduced hydrogen peroxide-induced oxidative stress and significantly increased dopamine levels in transgenic C. elegans.


Assuntos
Dopamina/metabolismo , Sulfeto de Hidrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Tionas/farmacologia , Tiofenos/farmacologia , Animais , Animais Geneticamente Modificados , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Caenorhabditis elegans/genética , Liberação Controlada de Fármacos , Oxirredução , Peptídeos/síntese química , Peptídeos/química , Fosfinas/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tionas/síntese química , Tionas/química , Tiofenos/síntese química , Tiofenos/química , alfa-Sinucleína/genética
5.
Chem Commun (Camb) ; 55(59): 8583-8586, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31274135

RESUMO

We present a near-infrared (NIR) fluorescent probe, NR-HNO, which was successfully applied to visualizing H2S/NO "crosstalk" by the fluorescence detection of nitroxyl with a fast response time (5 min) and a large Stokes shift (131 nm) in living cells and tissue; it was also used to image nitroxyl in live mice.


Assuntos
Compostos de Benzilideno/química , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/análise , Animais , Compostos de Benzilideno/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/efeitos da radiação , Humanos , Rim/metabolismo , Luz , Limite de Detecção , Fígado/metabolismo , Camundongos , Microscopia de Fluorescência/métodos , Nitritos/química , Óxidos de Nitrogênio/metabolismo , Espectrometria de Fluorescência/métodos
6.
Nat Commun ; 10(1): 2868, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253770

RESUMO

Prokaryotes and eukaryotes alike endogenously generate the gaseous molecule hydrogen sulfide (H2S). Bacterial H2S acts as a cytoprotectant against antibiotics-induced stress and promotes redox homeostasis. In E. coli, endogenous H2S production is primarily dependent on 3-mercaptopyruvate sulfurtransferase (3MST), encoded by mstA. Here, we show that cells lacking 3MST acquire a phenotypic suppressor mutation resulting in compensatory H2S production and tolerance to antibiotics and oxidative stress. Using whole genome sequencing, we identified a non-synonymous mutation within an uncharacterized LacI-type transcription factor, ycjW. We then mapped regulatory targets of YcjW and discovered it controls the expression of carbohydrate metabolic genes and thiosulfate sulfurtransferase PspE. Induction of pspE expression in the suppressor strain provides an alternative mechanism for H2S biosynthesis. Our results reveal a complex interaction between carbohydrate metabolism and H2S production in bacteria and the role, a hitherto uncharacterized transcription factor, YcjW, plays in linking the two.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Sulfeto de Hidrogênio/metabolismo , Fatores de Transcrição/metabolismo , Substituição de Aminoácidos , Antibacterianos/farmacologia , Mapeamento Cromossômico , DNA Bacteriano , Proteínas de Ligação a DNA/genética , Dissacarídeos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/fisiologia , Ligação Proteica , RNA Mensageiro , Regulon , Fatores de Transcrição/genética
7.
Food Chem Toxicol ; 131: 110543, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154084

RESUMO

A dual role of hydrogen sulfide (H2S) in inflammation is well-reported and recent studies demonstrated adipogenic effects of H2S in 3T3-L1 cells. Here, we aimed to investigate the effects of H2S on adipocyte differentiation and inflammation. H2S concentration in 3T3-L1 culture media was increased during adipocyte differentiation in parallel to adipogenic and Cth gene expression, and its inhibition using DL-Propargyl Glycine (PPG) impaired 3T3-L1 differentiation. GYY4137 and Na2S administration only in the first or in the last stage of adipocyte differentiation resulted in a significant increased expression of adipogenic genes. However, when GYY4137 or Na2S were administrated during all process no significant effects on adipogenic gene expression were found, suggesting that excessive H2S administration might exert negative effects on adipogenesis. In fact, continuous addition of Na2S, which resulted in Na2S excess, inhibited adipogenesis, whereas time-expired Na2S had no effect. In inflammatory conditions, GYY4137, but not Na2S, administration attenuated the negative effects of inflammation on adipogenesis and insulin signaling-related gene expression during adipocyte differentiation. In inflamed adipocytes, Na2S administration enhanced the negative effects of inflammatory process. Altogether these data showed that slow-releasing H2S improved adipocyte differentiation in inflammatory conditions, and that H2S proadipogenic effects depend on dose, donor and exposure time.


Assuntos
Adipócitos/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Sulfetos/farmacologia , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Adipogenia/fisiologia , Alquinos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Glicina/análogos & derivados , Glicina/farmacologia , Inflamação/fisiopatologia , Camundongos
8.
Georgian Med News ; (289): 135-139, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31215895

RESUMO

In the present study, we delineate the comparative effects of melatonin (MLT) on the metabolism of hydrogen sulfide in the liver and its influence on alterations in the antioxidant system caused by experimentally induced diabetes. Experiments were conducted on sexually mature university-bred male rats. Diabetes was induced by a single intraperitoneal injection of alloxan monohydrate solution. The animals were divided into the following groups: 1) control rats; 2) alloxan induced diabetic rats; 3) animals with diabetes which were introduced the melatonin. In case of diabetes mellitus the introduction of exogenous melatonin normalizes the hydrogen sulfide content and enzyme activity of its synthesis in the liver of rats possibly due to the activation of antioxidant enzymes protection, especially glutathione system that depends on sulfur-containing amino acids metabolism. Also the administration of MLT contributes increased activities of antioxidant enzymes in the liver, which demonstrates its effective antioxidant role in this organ. This protection on liver against oxidative stress might also partially have contributed to the hypoglycemic effect of MLT in diabetic rats.


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Glutationa , Sulfeto de Hidrogênio , Melatonina , Aloxano , Animais , Antioxidantes/farmacologia , Glutationa/metabolismo , Hidrogênio , Sulfeto de Hidrogênio/metabolismo , Fígado , Masculino , Melatonina/farmacologia , Estresse Oxidativo , Ratos Wistar
9.
Plant Sci ; 285: 34-43, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203892

RESUMO

Seed germination is a critical stage during the initiation of the plant lifecycle and is strongly affected by endogenous phytohormones and environmental stress. High temperature (HT) upregulates endogenous abscisic acid (ABA) to suppress seed germination, and ABA-INSENSITIVE 5 (ABI5) is the key positive regulator in the ABA signal-mediated modulation of seed germination. In plants, hydrogen sulfide (H2S) is a small gas messenger that participates in multiple physiological processes, but its role in seed germination thermotolerance has not been thoroughly elucidated to date. In this study, we found that H2S enhanced the seed germination rate under HT. Moreover, HT accelerates the efflux of the E3 ligase CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) from the nucleus to the cytoplasm, which results in increased nuclear accumulation of ELONG HYPCOTYL 5 (HY5) to activate the expression of ABI5 and thereby suppress seed germination. However, the H2S signal reversed the HT effect, as characterized by increased COP1 in the nucleus, which resulted in increased degradation of HY5 and reduced expression of ABI5 and thereby enhanced the seed germination thermotolerance. Thus, our findings reveal a novel role for the H2S signal in the modulation of seed germination thermotolerance through the nucleocytoplasmic partitioning of COP1 and the downstream HY5 and ABI5 pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Germinação/fisiologia , Sulfeto de Hidrogênio/metabolismo , Proteínas Nucleares/metabolismo , Sementes/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/fisiologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Núcleo Celular/enzimologia , Núcleo Celular/metabolismo , Giberelinas/metabolismo , Giberelinas/fisiologia , Temperatura Alta , Proteínas Nucleares/fisiologia , Reguladores de Crescimento de Planta/fisiologia , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Sementes/fisiologia , Transdução de Sinais/fisiologia , Termotolerância , Ubiquitina-Proteína Ligases/fisiologia
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 107-112, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250600

RESUMO

OBJECTIVE: To investigate the hypothesis that hydrogen could ameliorate cecal ligation and puncture (CLP)-induced lung injury of rats by inhibiting cystathionine-gamma-lyase/hydrogen sulfide (CSE/H2S) system. METHODS: A total number of 24 healthy male SD rats weighting 250~300 g were randomly divided into four groups (n=6 in each group): sham operation group(sham group), hydrogen-rich saline control group(H2 group), CLP group and hydrogen-rich saline treatment group(CLP+H2 group). The rats were treated with hydrogen-rich saline or saline 10 min before CLP or sham operation. At 8 h of sham or CLP operation, lung samples were obtained to detect the changes of the CSE/H2S system using biochemical and RT-PCR methods. In order to further confirm the role of H2S during hydrogen improve the lung injury of CLP rats, we also observed the effect of hydrogen-rich saline on the lung injury induced by H2S donor-sodium sodium hydrosulfide (NaHS). Thirty-two healthy male SD rats (250~300 g) were randomly divided into four groups (n=8 in each group): control group, H2S group, H2S+H2 group and H2 group. Saline(10 mg/kg) or NaHS(H2S donor, 56 µmol/kg) was injected intraperitoneally (10 mg/kg) respectively into rats in the control rats or H2S group. For rats in the H2S+H2 and H2 group, hydrogen-rich saline (10 mg/kg) was injected 10 min before saline or NaHS administration. Eight hours after the LPS saline or NaHS administration, lung coefficient, MDA content, and MPO activity were detected. The contents of TNF-α, IL-6 and IL-10 in lung tissue were measured, and the morphological changes of lung tissue were also observed. RESULTS: CSE/H2S system up-regulating were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly inhibited CSE/H2S system as indicated by significantly reduced H2S production in lung, along with a decreased CSE activity and CSE mRNA expression (all P<0.05). Importantly, the results showed that lung injury and lung tissue inflammation were observed in animals exposed to NaHS. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved histological changes in lung, significantly reduced index of quantitative assessment (IQA), MDA content and lung coefficient (all P<0.05). MPO activity in lung tissue was significantly reduced along with decreased productions of TNF-α and IL-6, and an increased production of IL-10 in the presence of hydrogen (all P<0.05), demonstrating antioxidant and anti-inflammatory effect of hydrogen in NaHS-induced ALI. CONCLUSION: These results indicate that hydrogen-rich saline peritoneal injection improves the lung injury induced by CLP operation. The therapeutic effects of hydrogen-rich saline may be related to suppressing the production of H2S.


Assuntos
Cistationina gama-Liase/metabolismo , Sulfeto de Hidrogênio/metabolismo , Hidrogênio/farmacologia , Lesão Pulmonar/terapia , Solução Salina/farmacologia , Animais , Ceco/cirurgia , Citocinas/metabolismo , Ligadura , Masculino , Punções , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Ecotoxicol Environ Saf ; 179: 222-231, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31048218

RESUMO

Hydrogen sulfide (H2S), a multifunctional gasotransmitter, participates in a wide range of cellular signal transduction and pathophysiological processes. Cystathionine gamma-lyase (CSE) acts as a major H2S-generating enzyme in peripheral organs and tissues. As a cysteine-rich and heavy metal-binding protein, metallothionein-1 (MT-1) is known to protect cells from various environmental stresses. Here we demonstrated that exposure of cadmium (Cd) induced oxidative stress, depleted intracellular thiols, and stimulated apoptotic cell death in mouse myoblast cells. CSE expression and H2S production were significantly enhanced by Cd treatment. NaHS, a well-known H2S donor, at physiologically relevant concentration significantly alleviated Cd-induced damage in both myoblasts and mouse skeletal muscles. In contrast, down-regulation of CSE/H2S system deteriorated Cd-stimulated oxidative stress and cell death. Exposure of the cells to Cd lead to increased expressions of metal regulatory transcription factor 1 and MT-1, while siRNA-mediated MT-1 knockdown alleviated Cd-induced CSE expression and caused more oxidative stress and cell death. In addition, H2S post-translationally modified MT-1 by S-sulfhydration and stabilized zinc-protein complex. Taken together, these data suggest that CSE/H2S system would protect myoblasts and skeletal muscles from Cd-induced damage by S-sufhydrating MT-1.


Assuntos
Cádmio/toxicidade , Cistationina gama-Liase/genética , Poluentes Ambientais/toxicidade , Sulfeto de Hidrogênio/metabolismo , Metalotioneína/metabolismo , Mioblastos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Mioblastos/metabolismo , Mioblastos/patologia , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Sulfetos/farmacologia
12.
Eur J Med Chem ; 176: 456-475, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128448

RESUMO

H2S donors are substitutes of H2S with various biological activities like inhibiting the inflammatory response and protecting myocardial cells from injury. In order to confirm whether the H2S donors have drug-like properties, two series thiophosphamide H2S donors were evaluated including toxicity, bioactivity and pharmacokinetic properties in vivo and in vitro. The following results were obtained. Firstly, all the compounds released H2S under measuring condition; with the increase of pH value, the H2S release rate of all the compounds decreased and the amount reduced, but pH value had little effect on the maximum release of H2S. Secondly, in the organs and tissues of rats, the compounds released H2S in the same way as in PBS. In plasma, compound 1 reached the Cmax after administration 55 min, and no compound 1 was detected after 12 h; for compound 18, the Cmax reached only after administration 100 min, and after 6 h, compound 18 was not detected; in organs and tissues, the H2S-release rates were different from those in PBS, but the mechanism of H2S release was the same. Thirdly, in the test of toxicity, all the compounds displayed low toxicities to 5 cancer cells and W138 cell lines; compounds 1 and 18 had slight effect on the physiological tissue and function of rat liver at low concentration; the compounds had almost no effect on the hatching rate, survival rate of zebrafish embryos, and the spontaneous movement of zebrafish embryos at below 0.5 µM, but when they were over 1 µM, the compounds displayed inhibitory effect in the manner of concentration dependence. Fourthly, in the course of anti-inflammatory test, all the tested compounds significantly reduced the level of TNF-α and increased the level of IL-10; when they were 100 µM, the levels of IL-10 were three times as high as those in the control group. Among them, compounds 10 and 18 displayed stronger activities than the others. In addition, the compounds protected H9c2 cells from injure and improved myocardial injury through anti-oxidation pathway. In summary, the compounds have druglike properties due to low toxicity, better activity and good pharmacokinetic property. Therefore, they have potential to be as candidates to investigate further.


Assuntos
Anti-Inflamatórios/farmacocinética , Cardiotônicos/farmacocinética , Sulfeto de Hidrogênio/metabolismo , Compostos Organotiofosforados/farmacocinética , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Cardiotônicos/síntese química , Cardiotônicos/química , Cardiotônicos/toxicidade , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/química , Concentração de Íons de Hidrogênio , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Modelos Químicos , Miocárdio/metabolismo , Compostos Organotiofosforados/síntese química , Compostos Organotiofosforados/química , Compostos Organotiofosforados/toxicidade , Células RAW 264.7 , Ratos Wistar , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Temperatura Ambiente , Teratogênios/síntese química , Teratogênios/química , Teratogênios/farmacocinética , Teratogênios/toxicidade , Peixe-Zebra
13.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071929

RESUMO

(1) The beneficial effects of hydrogen sulfide (H2S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H2S biosynthesis, previously used as a marker for H2S production, is dramatically increased in circulation in uremia, while H2S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H2S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H2S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine-ß-synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca2+ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid.


Assuntos
Alanina/análogos & derivados , Cálcio/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Sulfetos/farmacologia , Uremia/tratamento farmacológico , Alanina/química , Alanina/farmacologia , Aminoácidos Sulfúricos/efeitos dos fármacos , Aminoácidos Sulfúricos/metabolismo , Linhagem Celular , Cistationina beta-Sintase/genética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , MicroRNAs/genética , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , Oxirredução , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Sulfetos/química , Uremia/genética , Uremia/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
14.
Acta Histochem ; 121(5): 604-610, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31113654

RESUMO

Endogenous gaseous transmitters (nitric oxide, carbon monoxide, and hydrogen sulphide) form a special neuromodulation system mediating the development and modification of nerve centers. Here, we examined the localization of key gaseous transmitter enzymes: cystathionine ß-synthetase (CBS), cystathionine γ-lyase (CSE), heme oxygenase 2 (HO-2), and constitutive NO synthase (nNOS) in the fetal human retina at different stages of development. The number of CBS- and CSE-positive photoreceptors and intermediate retinal neurons was high in trimester I and gradually decreased to the end of trimester III. The number of HO-2-positive cells followed the same trend. The number of nNOS-positive intermediate retinal neurons and neurons within the ganglion cell layer showed the opposite dynamics with the peak in trimester III. The results are interpreted in terms of the role of gaseous transmitters in retinogenesis and cytoprotection.


Assuntos
Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Retina/embriologia , Retina/enzimologia , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Desenvolvimento Embrionário/fisiologia , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Imuno-Histoquímica , Óxido Nítrico Sintase/metabolismo
16.
Analyst ; 144(10): 3381-3388, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30984924

RESUMO

Hydrogen sulfide (H2S) exists in the cytosol and mitochondria of mammalian cells as a signaling molecule. Scientists have explored many important physiological functions of H2S, such as regulating vasodilator relaxation, protecting living cells and avoiding damage. The measurement of H2S is therefore necessary for exploring the biological function of cells and tissues. Herein, we report the design and synthesis of a new aggregation-induced emission luminogen (AIEgen) with greater conjugation and more positive charges, based on previous research on mitochondrial-targeted luminogens. The Indo-TPE-Indo can enter cells rapidly, as compared with an AIEgen with only one indolium (TPE-indo), and can selectively recognize HS- in mitochondria with the nucleophilic reaction of indolium and HS-. The linear range (1-100 µM) of HS- sensing can satisfy the requirement for HS- concentration in living cells and tumors.


Assuntos
Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Indóis/química , Mitocôndrias/metabolismo , Estilbenos/química , Animais , Estabilidade de Medicamentos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana , Humanos , Sulfeto de Hidrogênio/metabolismo , Indóis/síntese química , Indóis/efeitos da radiação , Luz , Células MCF-7 , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Neoplasias/metabolismo , Estilbenos/síntese química , Estilbenos/efeitos da radiação
17.
Biomed Pharmacother ; 112: 108736, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970526

RESUMO

INTRODUCTION: The purpose of the experiment was to survey the therapeutic function of resveratrol (RES)-loaded poly(ethylene glycol)-poly(phenylalanine) (PEG-PPhe) on intestinal ischemia/reperfusion injury (II/RI) via the interaction between CSE/H2S and iNOS/NO compared to free RES in diabetic rats. METHODS: Diabetic rats were pretreated with 20 mg/kg of RES or the RES/PEG-PPhe complex and then subjected to 1 h of ischemia and 3 h of reperfusion. Blood and intestines were collected, intestinal pathological injury was estimated, and the contents of body weight, weights of different tissues, blood glucose, serum insulin, HOMA index, serum nitric oxide (NO) and serum sulfureted hydrogen (H2S) were observed. The dry/wet intestine ratios, the activity of superoxide dismutase (SOD); the contents of methane dicarboxylic aldehyde (MDA), glutathione (GSH), H2S, and NO; and the concentrations of inducible nitric oxide synthase (iNOS) and cystathionine-γ-lyase (CSE) were observed in the intestinal tissues. RESULTS: A significant reduction of weights of different tissues, blood glucose, pathological damage, dry/wet ratios, MDA, NO, iNOS expression and a significant increasement of body weight, serum insulin, HOMA index, SOD, GSH, H2S, CSE expression were observed in both treatment groups. However, a greater reduction of weights of different tissues, blood glucose (7.49-13.49 mmol/L for 72 h vs. the control) and pathological damage, iNOS expression, dry/wet ratios (6.14 ± 0.29 vs. 8.51 ± 0.42), MDA (5.01 ± 0.71 nmol vs. 9.98 ± 0.67 nmol), NO (0.52 ± 0.09 µmol vs. 0.99 ± 0.08 µmol in intestinal tissue; 19.29 ± 0.89 µmol vs. 45.23 ± 1.17 µmol in serum) was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all); a greater increasement of body weight, serum insulin, HOMA index, SOD (39.79±1.78 U vs. 11.84 ± 1.02 U), GSH (31.25 ± 1.19 mg vs. 10.13 ± 0.64 mg), H2S (39.52 ± 1.32 nmol vs. 13.02 ± 1.03 nmol in intestinal tissue; 9.78 ± 0.79 µmol vs. 3.11 ± 0.85 µmol in serum), CSE expression was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all). In addition, aminoguanidine (AMI, iNOS inhibitor) reduced I/R injury, and dl-propargylglycine (PAG, CSE inhibitor) increased I/R injury. CONCLUSIONS: The interaction between CSE/H2S and the iNOS/NO-mediated resveratrol/poly(ethylene glycol)-poly(phenylalanine) complex alleviates intestinal ischemia/reperfusion injuries in diabetic rats.


Assuntos
Diabetes Mellitus Experimental/complicações , Portadores de Fármacos/química , Intestinos/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/uso terapêutico , Animais , Cistationina gama-Liase/metabolismo , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Sulfeto de Hidrogênio/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Substâncias Protetoras/administração & dosagem , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Resveratrol/administração & dosagem
18.
Nat Commun ; 10(1): 1609, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962433

RESUMO

Bacterial degradation of organosulfonates plays an important role in sulfur recycling, and has been extensively studied. However, this process in anaerobic bacteria especially gut bacteria is little known despite of its potential significant impact on human health with the production of toxic H2S. Here, we describe the structural and biochemical characterization of an oxygen-sensitive enzyme that catalyzes the radical-mediated C-S bond cleavage of isethionate to form sulfite and acetaldehyde. We demonstrate its involvement in pathways that enables C2 sulfonates to be used as terminal electron acceptors for anaerobic respiration in sulfate- and sulfite-reducing bacteria. Furthermore, it plays a key role in converting bile salt-derived taurine into H2S in the disease-associated gut bacterium Bilophila wadsworthia. The enzymes and transporters in these anaerobic pathways expand our understanding of microbial sulfur metabolism, and help deciphering the complex web of microbial pathways involved in the transformation of sulfur compounds in the gut.


Assuntos
Acetiltransferases/metabolismo , Proteínas de Bactérias/metabolismo , Desulfovibrio/metabolismo , Sulfeto de Hidrogênio/toxicidade , Taurina/metabolismo , Acetiltransferases/genética , Acetiltransferases/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Ácidos e Sais Biliares/metabolismo , Bilophila/metabolismo , Ensaios Enzimáticos , Microbioma Gastrointestinal/fisiologia , Sulfeto de Hidrogênio/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mercaptoetanol/análogos & derivados , Mercaptoetanol/metabolismo , Redes e Vias Metabólicas/fisiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Enxofre/metabolismo
19.
Toxicol Lett ; 310: 39-50, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30980911

RESUMO

This study explored the role of gasotransmitters in lead-induced nephrotoxicity. Long-term exposure of rats to lead resulted in its accumulation in kidney. The accumulated metal impaired kidney function and structure. Lead intoxication resulted in oxidative stress, inflammation and apoptosis in kidney. In addition, it resulted in nitric oxide (NO) overproduction and decrease in hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in kidney. Inhibition of NO overproduction by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and CO level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of kidney function and structure. These agents inhibited lead-intoxication induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of H2S level and HO-1 concentration. Also, concomitant treatment with these agents inhibited lead intoxication-induced increase in protein expressions of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine- γ-lyase (CSE) in kidney. The NO donor, L-arginine and the H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively produced opposite effects and aggravated the toxic effects of lead. These results demonstrate, for the first time, that gasotransmitters play an important role in lead-induced nephrotoxicity.


Assuntos
Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Óxido Nítrico/metabolismo , Compostos Organometálicos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citocinas/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
20.
J Ethnopharmacol ; 236: 136-146, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30851368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice and Yuanhua are both famous herbs in Traditional Chinese Medicine (TCM), and their combination is used by some TCM doctors to treat renal and gastrointestinal diseases as well as tumors. On the other hand, the compatibility theory of TCM warns that toxic effects might be triggered by Licorice-Yuanhua combination. The usability of Licorice-Yuanhua combination has long been controversial due to lack of evidence and mechanism illustration. Colonic hydrogen sulfide (H2S) metabolism imbalance is closely related with colonic inflammation, tumor promotion and many other diseases. AIM OF THE STUDY: This study was carried out to investigate if licorice-Yuanhua combination could induce potential toxic effects in the aspect of colonic H2S metabolism. MATERIALS AND METHODS: Normal mice were treated with high or low doses of Licorice, Yuanhua and Licorice-Yuanhua combination. Fecal H2S concentration was measured by colorimetric method, colon sulfomucin production was compared through tissue staining, fecal microbiota and microbial metagenomes were analyzed by 16S rDNA sequencing and data mining. RESULTS: Data shows that although licorice cannot change colonic H2S concentration, it can exacerbate Yuanhua induced H2S rising. Licorice or Yuanhua increases colon sulfomucin production, and their combination further enhances this effect. 16S rDNA sequencing analysis revealed that licorice or Yuanhua has little influence on gut microbiota, however, licorice-Yuanhua combination can impact gut microbiota structural balance and increase the abundance of Desulfovibrio genus and other related genera. Moreover, the combination extensively changes microbial metagenomes, influencing 1172 genes that cannot be changed by individual licorice or Yuanhua. By searching in KEGG database, ten genes are annotated with H2S producing gene, and these genes are remarkably increased by licorice-Yuanhua combination, more significantly than licorice or Yuanhua. CONCLUSIONS: This study provides evidences and mechanisms for licorice induced risks, which is related with colonic H2S metabolism disturbance, gut microbiota and microbial metagenomes. More risk assessment should be evaluated when licorice was used in combination with foods, herbs or drugs. The study provides an example where healthy risks can be induced by combination of food additive, herbs or drugs, through regulating gut microbiota and its metagenomes.


Assuntos
Colo/efeitos dos fármacos , Daphne/química , Medicamentos de Ervas Chinesas/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Glycyrrhiza/química , Sulfeto de Hidrogênio/metabolismo , Animais , Colo/metabolismo , Colo/microbiologia , Desulfovibrio/efeitos dos fármacos , Desulfovibrio/genética , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/isolamento & purificação , Fezes/química , Flores/química , Microbioma Gastrointestinal/genética , Sulfeto de Hidrogênio/análise , Masculino , Medicina Tradicional Chinesa , Metagenoma/genética , Camundongos Endogâmicos ICR , Raízes de Plantas/química
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