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1.
J Environ Pathol Toxicol Oncol ; 39(3): 281-290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865918

RESUMO

Objective-To investigate cystathionine ß synthase (CBS)/hydrogen sulfide (H2S) signaling in multiple myeloma (MM) patients and to identify its effect on the proliferation of U266 cells. Methods-Bone marrow samples of 19 MM patients and 23 healthy donors were collected. qRT-PCR was performed to measure the mRNA expression levels of H2S synthases, cystathionine ß synthase, and cystathionine γ lyase. ELISA assays quantified the amount of H2S produced by the two enzymes CBS and CSE. CCK-8 experiment was used to investigate the influence of the CBS inhibitor amino oxyacetic acid and the CSE inhibitor propargylglycine on the proliferation of U266 cells. Flow cytometry and western blotting were performed to determine the effects of AOAA, PAG, and NaHS on cell cycle distribution as well as Caspase-3 and Bcl-2 expression. Results-Patients with MM had higher level of CBS compared with healthy donors. AOAA significantly inhibited cell proliferation in both a time and concentration dependent characteristic, whereas PAG does not. After 24 hours of treatment, AOAA significantly elevated the G0/G1 phase proportion of cells, and reduced the cell distribution in both S and G2/M phases, while NaHS accelerated cell cycle progression by reducing the relative number of cells in G0/G1 phase and increasing the proportion of cells in the G2/M phase. Moreover, AOAA abolished the impact of NaHS on cell cycle progression of U266 cells. AOAA treatment also led to a significant decrease in Bcl-2 expression and dramatic increase in Caspase-3 expression, though NaHS reversed these effects. Conclusion-CBS/H2S system might have a certain effect on the proliferation and apoptosis of MM cells.


Assuntos
Apoptose , Proliferação de Células , Cistationina beta-Sintase/metabolismo , Sulfeto de Hidrogênio/metabolismo , Mieloma Múltiplo/metabolismo , Adulto , Idoso , Alquinos/farmacologia , Ácido Amino-Oxiacético/farmacologia , Apoptose/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cistationina beta-Sintase/antagonistas & inibidores , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Glicina/análogos & derivados , Glicina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Transdução de Sinais
2.
Yakugaku Zasshi ; 140(9): 1119-1128, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879244

RESUMO

Humans are exposed to various xenobiotic electrophiles on a daily basis. Electrophiles form covalent adducts with nucleophilic residues of proteins. Redox signaling, which consists of effector molecules (e.g., kinases and transcription factors) and redox sensor proteins with low pKa cysteine residues, is involved in cell survival, cell proliferation, quality control of cellular proteins and oxidative stress response. Herein, we showed that at a low dose, xenobiotic electrophiles selectively modified redox sensor proteins through covalent modification of their reactive thiols, resulting in activation of a variety of redox signaling pathways. However, increasing the dose of xenobiotic electrophiles caused non-selective and extensive modification of cellular proteins involved in toxicity. Of interest, reactive sulfur species (RSS), such as hydrogen sulfide (H2S), cysteine persulfide (CysSSH), glutathione persulfide (GSSH) and even synthetic polysulfide (e.g., Na2S4), readily captured xenobiotic electrophiles, forming their sulfur adducts, which was associated with inactivation of the electrophiles. Our findings suggest that an adaptive response through redox signaling activation and RSS-mediated electrophile capturing is involved in the regulation of electrophilic stress.


Assuntos
Cisteína/análogos & derivados , Dissulfetos/metabolismo , Glutationa/análogos & derivados , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Cisteína/metabolismo , Glutationa/metabolismo , Humanos , Compostos de Sulfidrila/metabolismo , Xenobióticos/metabolismo
4.
Ecotoxicol Environ Saf ; 203: 110978, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678757

RESUMO

In this study, hydroponic experiments were conducted to elucidate mechanism(s) that are associated with differential effects of low (5 µM) and high (25 µM) dose of cadmium (Cd) stress in tomato. Furthermore, emphasis has also been focused on any involvement of endogenous hydrogen sulfide (H2S) in differential behaviour of low and high doses of Cd stress. At low dose of Cd, root growth i.e. root fresh weight, length and fitness did not significantly alter when compared to the control seedlings. Though at low dose of Cd, cellular accumulation of Cd was slightly increased but this was accompanied by higher endogenous H2S and phytochelatins, L-cysteine desulfhydrase (DES) activity, activities of glutathione biosynthetic and AsA-GSH cycle enzymes, and maintained redox status of ascorbate and glutathione. However, addition of hypotaurine (HT, a scavenger of H2S) resulted in greater toxicity, even at low dose of Cd, and these responses resembled with higher dose of Cd stress such as greater decline in root growth, endogenous H2S and phytochelatins, activities of DES, glutathione biosynthesis and AsA-GSH cycle enzymes, disturbed redox status of ascorbate and glutathione which collectively led to higher oxidative stress in tomato roots. Moreover, addition of HT with higher dose of Cd also further enhanced its toxicity. Collectively, the results showed that differential behaviour of low and high dose of Cd stress is mediated by differential regulation of biochemical attributes in which endogenous H2S has a crucial role.


Assuntos
Cádmio/toxicidade , Sulfeto de Hidrogênio/metabolismo , Lycopersicon esculentum/efeitos dos fármacos , Fitoquelatinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Poluentes do Solo/toxicidade , Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(27): 15599-15608, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571930

RESUMO

2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling by microbes, thus, play important roles in the biogeochemical sulfur cycle. However, DHPS degradative pathways in the anaerobic biosphere are not well understood. Here, we report the discovery and characterization of two O2-sensitive glycyl radical enzymes that use distinct mechanisms for DHPS degradation. DHPS-sulfolyase (HpsG) in sulfate- and sulfite-reducing bacteria catalyzes C-S cleavage to release sulfite for use as a terminal electron acceptor in respiration, producing H2S. DHPS-dehydratase (HpfG), in fermenting bacteria, catalyzes C-O cleavage to generate 3-sulfopropionaldehyde, subsequently reduced by the NADH-dependent sulfopropionaldehyde reductase (HpfD). Both enzymes are present in bacteria from diverse environments including human gut, suggesting the contribution of enzymatic radical chemistry to sulfur flux in various anaerobic niches.


Assuntos
Alcanossulfonatos/metabolismo , Anaerobiose , Bactérias/enzimologia , Proteínas de Bactérias/metabolismo , Microbioma Gastrointestinal/fisiologia , Biologia Computacional , Ensaios Enzimáticos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/toxicidade , Metilglucosídeos/metabolismo , Enxofre/metabolismo
6.
Proc Natl Acad Sci U S A ; 117(28): 16424-16430, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32586956

RESUMO

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S)-a toxicant that impairs mitochondrial function-across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H2S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H2S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H2S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and-in some instances-codons are implicated in H2S adaptation in lineages that span 40 million years of evolution.


Assuntos
Evolução Molecular , Mitocôndrias/metabolismo , Poecilia/fisiologia , Adaptação Fisiológica , Animais , Ecossistema , Ambientes Extremos , Genoma , Sulfeto de Hidrogênio/metabolismo , Mitocôndrias/genética , Filogenia , Poecilia/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-32474386

RESUMO

It was aimed to examine the role of gibberellic acid (GA) induced production of hydrogen sulfide (H2S) in alleviating boron toxicity (BT) in tomato plants. Two weeks after germination, a solution consisting of GA (100 mg L-1) was sprayed once a week for 14 days to the leaves of cv. "SC 2121" of tomato under BT stress (BT; 2.0 mM). Before starting BT treatment, half of the seedlings were retained in a solution containing a scavenger of H2S, 0.1 mM hypotaurine (HT), for 12 h. Boron toxicity led to a substantial decrease in dry biomass, leaf water potential, leaf relative water content, chlorophyll a, chlorophyll b, photosynthetic quantum yield (Fv/Fm), ascorbate (AsA) and glutathione (GSH) in the tomato plants. However, it increased the accumulation of hydrogen peroxide (H2O2), malondialdehyde (MDA), endogenous hydrogen sulfide (H2S), and free proline as well as the activities of catalase, superoxide dismutase and peroxidase. The supplementation of GA mitigated BT by increasing the endogenous H2S, and leaf Ca2+ and K+, and reducing the contents of leaf H2O2, MDA, and B as well as membrane leakage. GA-induced BT tolerance was further enhanced by the supplementation of sodium hydrosulfide (0.2 mM NaHS), an H2S donor. A scavenger of H2S, hypotaurine (0.1 mM HT) was supplied along with the GA and NaHS treatments to assess if H2S was involved in GA-induced BT tolerance of tomato plants. Addition of HT reversed the beneficial effect of GA on oxidative stress and antioxidant defence system by reducing the endogenous H2S without changing L-DES activity, suggesting that H2S participates in GA-induced tolerance to BT of tomato plants.


Assuntos
Boro/toxicidade , Giberelinas/farmacologia , Sulfeto de Hidrogênio/metabolismo , Lycopersicon esculentum/efeitos dos fármacos , Antioxidantes , Clorofila , Peróxido de Hidrogênio , Lycopersicon esculentum/metabolismo , Malondialdeído , Estresse Oxidativo , Plântula
8.
Prostate ; 80(12): 962-976, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32511787

RESUMO

OBJECTIVE: The broad goal of the research described in this study was to investigate the contributions of selenium-binding protein 1 (SBP1) loss in prostate cancer development and outcome. METHODS: SBP1 levels were altered in prostate cancer cell lines and the consequences on oxygen consumption, expression of proteins associated with energy metabolism, and cellular transformation and migration were investigated. The effects of exposing cells to the SBP1 reaction products, H2 O2 and H2 S were also assessed. In silico analyses identified potential HNF4α binding sites within the SBP1 promoter region and this was investigated using an inhibitor specific for that transcription factor. RESULTS: Using in silico analyses, it was determined that the promoter region of SBP1 contains putative binding sites for the HNF4α transcription factor. The potential for HNF4α to regulate SBP1 expression was supported by data indicating that HNF4α inhibition resulted in a dose-response increase in the levels of SBP1 messenger RNA and protein, identifying HNF4α as a novel negative regulator of SBP1 expression in prostate cancer cells. The consequences of altering the levels of SBP1 were investigated by ectopically expressing SBP1 in PC-3 prostate cancer cells, where SBP1 expression attenuated anchorage-independent cellular growth and migration in culture, both properties associated with transformation. SBP1 overexpression reduced oxygen consumption in these cells and increased the activation of AMP-activated protein kinase (AMPK), a major regulator of energy homeostasis. In addition, the reaction products of SBP1, H2 O2 , and H2 S also activated AMPK. CONCLUSIONS: Based on the obtained data, it is hypothesized that SBP1 negatively regulates oxidative phosphorylation (OXPHOS) in the healthy prostate cells by the production of H2 O2 and H2 S and consequential activation of AMPK. The reduction of SBP1 levels in prostate cancer can occur due to increased binding of HNF4α, acting as a transcriptional inhibitor to the SBP1 promoter. Consequently, there is a reduction in H2 O2 and H2 S-mediated signaling, inhibition of AMPK, and stimulation of OXPHOS and building blocks of biomolecules needed for tumor growth and progression. Other effects of SBP1 loss in tumor cells remain to be discovered.


Assuntos
Neoplasias da Próstata/metabolismo , Proteínas de Ligação a Selênio/metabolismo , Linhagem Celular Tumoral , Transformação Celular Viral , Metilação de DNA , Progressão da Doença , Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Glucose/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Masculino , Fosforilação Oxidativa , Consumo de Oxigênio , Células PC-3 , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Quinases/metabolismo , Proteínas de Ligação a Selênio/deficiência , Proteínas de Ligação a Selênio/genética , Frações Subcelulares/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-32515982

RESUMO

The outbreak of COVID-19 pneumonia caused by a new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is posing a global health emergency and has led to more than 380,000 deaths worldwide. The cell entry of SARS-CoV-2 depends on two host proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). There is currently no vaccine available and also no effective drug for the treatment of COVID-19. Hydrogen sulfide (H2S) as a novel gasotransmitter has been shown to protect against lung damage via its anti-inflammation, antioxidative stress, antiviral, prosurvival, and antiaging effects. In light of the research advances on H2S signaling in biology and medicine, this review proposed H2S as a potential defense against COVID-19. It is suggested that H2S may block SARS-CoV-2 entry into host cells by interfering with ACE2 and TMPRSS2, inhibit SARS-CoV-2 replication by attenuating virus assembly/release, and protect SARS-CoV-2-induced lung damage by suppressing immune response and inflammation development. Preclinical studies and clinical trials with slow-releasing H2S donor(s) or the activators of endogenous H2S-generating enzymes should be considered as a preventative treatment or therapy for COVID-19.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Sulfeto de Hidrogênio/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Sulfeto de Hidrogênio/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Serina Endopeptidases/metabolismo , Transdução de Sinais
10.
Life Sci ; 255: 117834, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454158

RESUMO

AIMS: Hydrogen sulfide (H2S) is shown in ocular tissues and suggested to involve in the regulation of retinal circulation. However, the mechanism of H2S-induced relaxation on retinal artery is not clarified yet. Herein, we aimed to evaluate the role of several calcium (Ca2+) signaling and Ca2+ sensitization mechanisms in the relaxing effect of H2S donor, NaHS, on retinal arteries. MATERIALS AND METHODS: Relaxing effects of NaHS (10-5-3 × 10-3M) were determined on precontracted retinal arteries in Ca2+ free medium as well as in the presence of the inhibitors of Ca2+ signaling and Ca2+ sensitization mechanisms. Additively, Ca2+ sensitivity of the contractile apparatus were evaluated by CaCl2-induced contractions in the presence of NaHS (3 × 10-3M). Functional experiments were furtherly assessed by protein and/or mRNA expressions, as appropriate. KEY FINDINGS: The relaxations to NaHS were preserved in Ca2+ free medium while NaHS pretreatment decreased the responsiveness to CaCl2. The inhibitors of plasmalemmal Ca2+-ATPase, sarcoplasmic-endoplasmic reticulum Ca2+-ATPase, Na+-Ca2+ ion-exchanger and myosin light chain kinase (MLCK) unchanged the relaxations to NaHS. Likewise, Ca2+ sensitization mechanisms including, rho kinase, protein kinase C and tyrosine kinase were unlikely to mediate the relaxation to NaHS in retinal artery. Whereas, a marked reduction was determined in NaHS-induced relaxations in the presence of MLCP inhibitor, calyculin A. Supportively, NaHS pretreatment significantly reduced phosphorylation of MYPT1-subunit of MLCP. SIGNIFICANCE: The relaxing effect of NaHS in retinal artery is likely to be related to the activation of MLCP and partly, to decrement in Ca2+ sensitivity of contractile apparatus.


Assuntos
Cálcio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Artéria Retiniana/metabolismo , Animais , Cloreto de Cálcio/administração & dosagem , Sinalização do Cálcio/fisiologia , Bovinos , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Feminino , Masculino , Fosforilação/fisiologia , Sulfetos/administração & dosagem , Sulfetos/farmacologia
11.
Life Sci ; 254: 117699, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437793

RESUMO

AIMS: Ischemia/reperfusion (I/R) injury largely limits the efficacy of revascularization in acute myocardial infarction. Long noncoding RNA (lncRNA) Oprm1 is protective in cerebral I/R injury. This study aimed to investigate the effect of lncRNA Oprm1 on myocardial I/R injury and its mechanism. MAIN METHODS: We ligated and then released the left anterior descending coronary artery of adult male rats to build the I/R model in vivo. At the same time, an H9c2 cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, histology, TUNEL staining, cell viability, and vital protein expression was conducted and compared. KEY FINDINGS: LncRNA Oprm1 was significantly down-regulated in the I/R injury model. When administered with the AAV9-Oprm1 vector, the myocardial injury and cardiac function were mitigated and preserved, with apoptosis reduced. The cystathionine-γ-lyase (CSE) expression and hydrogen sulfide (H2S) expression were increased. The dual-luciferase reporter gene revealed the targeted relationship between lncRNA Oprm1 and miR-30b-5p. In H9c2 cardiomyocytes models, the miR-30b-5p blocked the protective effect of lncRNA Oprm1 on H/R injury, when Bcl-2, Bcl-xl was down-regulated, and HIF-1α, Bnip-3, Caspase-3, and Caspase-9 up-regulated. SIGNIFICANCE: LncRNA Oprm1can competitively combines with miR-30b-5p, which down-regulates the expression of CSE. When administered with lncRNA Oprm1, increased endogenous H2S can reduce apoptosis and protect the myocardium from I/R injury via activating PI3K/Akt pathway and inhibiting HIF1-α activity.


Assuntos
Cistationina gama-Liase/metabolismo , Sulfeto de Hidrogênio/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , RNA Longo não Codificante/genética , Receptores Opioides mu/genética , Animais , Modelos Animais de Doenças , Humanos , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/metabolismo
12.
Life Sci ; 256: 117855, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473245

RESUMO

OBJECTIVE: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. METHODS: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) were recorded during baseline and following myocardial IR injury. In addition, infarct size as well as mRNA expression of H2S- and nitric oxide (NO)-producing enzymes were measured. RESULTS: In diabetic rats, NaSH only at doses of 0.56 and 1.6 mg/kg increased recovery of LVDP (16% and 42%), +dp/dt (25% and 35%) and -dp/dt (23% and 32%) as well as decreased infarct size (44% and 35%). At these doses, NaSH increased expressions of cystathionine γ-lyase (CSE) (440% and 271%) and endothelial NO synthase (eNOS) (232% and 148%) but it decreased the expressions of inducible NOS (iNOS) (55% and 71%). NaSH at 0.28, 2.8 and 5.6 mg/kg had no significant effects on these parameters. CONCLUSION: NaSH had a bell-shaped cardioprotective effect against myocardial IR injury in rats with T2D. Higher tolerance to IR injury in heart isolated from type 2 diabetic rats treated with intermediate doses of NaSH is associated with higher CSE-derived H2S and eNOS-derived NO as well as lower iNOS-derived NO.


Assuntos
Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Sulfetos/farmacologia , Animais , Cardiotônicos/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Sulfeto de Hidrogênio/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/complicações , Ratos , Ratos Wistar , Estreptozocina , Sulfetos/administração & dosagem
13.
Life Sci ; 252: 117661, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32305523

RESUMO

AIMS: Hydrogen sulfide (H2S) as a novel gasotransmitter can be endogenously produced in liver by cystathionine gamma-lyase (CSE). The dysfunctions of CSE/H2S system have been linked to various liver diseases. Acetyl-CoA is the key intermediate from the metabolism of lipid. This study examined the roles of H2S in hepatic acetyl-CoA and lipid metabolism. MATERIALS AND METHODS: Both in vitro cell model and in vivo animal model of lipid accumulation were used in this study. Western blotting and real-time PCR were used for analysis of protein and mRNA expression. Acetyl-CoA was analyzed by a coupled enzyme assay, and lipid accumulation was observed with Oil Red O staining. KEY FINDINGS: Incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production, promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS or cysteine reduced acetyl-CoA contents and lipid accumulation, while blockage of CSE activity promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcriptions of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expressions of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissues from CSE knockout mice when compared with wild-type mice. SIGNIFICANCE: CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion.


Assuntos
Acetilcoenzima A/metabolismo , Cistationina gama-Liase/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Sulfeto de Hidrogênio/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Cistationina gama-Liase/genética , Modelos Animais de Doenças , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
14.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 792-800, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32347073

RESUMO

Stomatal density is important for crop yield. In this paper, we studied the epidermal pattern factors (EPFs) related to stomatal development. Prokaryotic expression vectors were constructed to obtain EPFs. Then the relationship between EPFs and hydrogen sulfide (H2S) was established. First, AtEPF1, AtEPF2 and AtEPFL9 were cloned and constructed to pET28a vectors. Then recombinant plasmids pET28a-AtEPF1, pET28a-AtEPF2 and pET28a-AtEPFL9 were digested and sequenced, showing successful construction. Finally, they were transformed into E. coli BL21(DE3) separately and induced to express by isopropyl ß-D-galactoside (IPTG). The optimized expression conditions including IPTG concentration (0.5, 0.3 and 0.05 mmol/L), temperature (28 °C, 28 °C and 16 °C) and induction time (16 h, 16 h and 20 h) were obtained. The bands of purified proteins were about 18 kDa, 19 kDa and 14.5 kDa, respectively. In order to identify their function, the purified AtEPF2 and AtEPFL9 were presented to Arabidopsis thaliana seedlings. Interestingly, the H2S production rate decreased or increased compared with the control, showing significant differences. That is, EPFs affected the production of endogenous H2S in plants. These results provide a foundation for further study of the relationship between H2S and EPFs on stomatal development, but also a possible way to increase the yield or enhance the stress resistance.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Escherichia coli , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/isolamento & purificação , Proteínas de Arabidopsis/metabolismo , Escherichia coli/genética , Vetores Genéticos/genética , Sulfeto de Hidrogênio/metabolismo , Plasmídeos/genética , Plântula/metabolismo
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 118-120, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148244

RESUMO

OBJECTIVE: Sepsis is an organ dysfunction that endangers a patient's life caused by an imbalanced infection response, and is a clinically critical illness. Despite a deep understanding of the pathogenesis of sepsis, there has been no significant improvement in sepsis mortality during clinical treatment at home and abroad. In recent years, the role of autophagy in the pathogenesis of sepsis has become a new research point in the field of medical research. Autophagy may protect the body by removing pathogenic microorganisms, neutralizing microbial toxins, and regulating cytokine release in sepsis. Studies have shown that autophagy plays a role in heart and lung organ dysfunction and inflammatory immune response in sepsis. Studies have also shown that hydrogen sulphide (H2S) can activate autophagy through multiple signaling pathways, such as adenylate-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), phosphoinositide 3 kinase/Akt/mTOR (PI3K/Akt/mTOR), liver kinase B1/STE20 related adapter protein/mouse protein 25 (LKB1/STRAD/MO25) and microRNA-30c (miR-30c), etc. signaling pathways. This article reviewed the effects of H2S on autophagy-related genes Beclin-1 and microtubule-associated protein light 3 chain (LC3) on intestinal function of sepsis in order to explore the H2S-mediated autophagy gene expression in pus. The protective role of autophagy gene for intestinal dysfunction provides a new strategy for the treatment of sepsis in the future.


Assuntos
Autofagia/genética , Sulfeto de Hidrogênio/metabolismo , Sepse/genética , Transdução de Sinais , Animais , Humanos
16.
Adv Exp Med Biol ; 1219: 335-353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130707

RESUMO

Hydrogen sulfide (H2S), while historically perceived merely as a toxicant, has progressively emerged as a key regulator of numerous processes in mammalian physiology, exerting its signaling function essentially through interaction with and/or modification of proteins, targeting mainly cysteine residues and metal centers. As a gaseous signaling molecule that freely diffuses across aqueous and hydrophobic biological milieu, it has been designated the third 'gasotransmitter' in mammalian physiology. H2S is synthesized and detoxified by specialized endogenous enzymes that operate under a tight regulation, ensuring homeostatic levels of this otherwise toxic molecule. Indeed, imbalances in H2S levels associated with dysfunctional H2S metabolism have been growingly correlated with various human pathologies, from cardiovascular and neurodegenerative diseases to cancer. Several cancer cell lines and specimens have been shown to naturally overexpress one or more of the H2S-synthesizing enzymes. The resulting increased H2S levels have been proposed to promote cancer development through the regulation of various cancer-related processes, which led to the interest in pharmacological targeting of H2S metabolism. Herein are summarized some of the key observations that place H2S metabolism and signaling pathways at the forefront of the cellular mechanisms that support the establishment and development of a tumor within its complex and challenging microenvironment. Special emphasis is given to the mechanisms whereby H2S helps shaping cancer cell bioenergetic metabolism and affords resistance and adaptive mechanisms to hypoxia.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Microambiente Tumoral , Animais , Humanos , Neoplasias/enzimologia
17.
Nihon Yakurigaku Zasshi ; 155(2): 74-79, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115481

RESUMO

Recently, hydrogen sulfide (H2S) has been recognized as the third gasotransmitter besides nitric oxide and carbon monoxide, and it has been reported that H2S exhibits various physiological functions such as neuromodulation and vasorelaxation. In the lower urinary tract (bladder and prostate), it is reported that donors of H2S induce contraction of the rat detrusor and relaxation of the pig bladder neck. These reports suggest a possibility that H2S may have site-specific effects on the bladder. However, the detailed functions of H2S in each part of the bladder are still unclear. In addition, there is no report showing physiological roles of H2S in the prostate. In this article, we will review the distribution of enzymes related to H2S biosynthesis and physiological roles of H2S in the lower urinary tract based on reports from our and other groups. We will also introduce a possibility that H2S can be a new therapeutic target against lower urinary tract symptoms (LUTS) based on our data from spontaneously hypertensive rats (SHRs), which develop hypertension-mediated LUTS.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Próstata/fisiologia , Bexiga Urinária/fisiologia , Animais , Masculino , Ratos , Ratos Endogâmicos SHR , Suínos
18.
J Insect Sci ; 20(2)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186739

RESUMO

Hydrogen sulfide (H2S) is a highly poisonous gas with an unpleasant smell of rotten eggs. Previous studies of H2S have primarily focused on its effects on mammalian nervous and respiratory systems. In this study, silkworm developmental parameters and changes in metabolites in response to H2S exposure were investigated using a hemolymph metabolomic approach, based on liquid chromatography-mass spectrometry (LC-MS). The developmental parameters, body weight, cocoon weight, cocoon shell weight, and cocoon shell ratio, were noticeably increased following H2S exposure, with the greatest effects observed at 7.5-µM H2S. Metabolites upregulated under H2S exposure (7.5 µM) were related to inflammation, and included (6Z, 9Z, 12Z)-octadecatrienoic acid, choline phosphate, and malic acid, while hexadecanoic acid was downregulated. Identified metabolites were involved in biological processes, including pyrimidine, purine, and fatty acid metabolism, which are likely to affect silk gland function. These results demonstrate that H2S is beneficial to silkworm development and alters metabolic pathways related to spinning function and inflammation. The present study provides new information regarding the potential functions of H2S in insects and metabolic pathways related to this phenomenon.


Assuntos
Bombyx/crescimento & desenvolvimento , Sulfeto de Hidrogênio/metabolismo , Animais , Bombyx/efeitos dos fármacos , Bombyx/metabolismo , Cromatografia Líquida , Hemolinfa/metabolismo , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Espectrometria de Massas , Metabolômica
19.
J Plant Res ; 133(3): 393-407, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32200466

RESUMO

Hydrogen sulfide (H2S) is an important gaseous molecule responding to osmotic stress in plant. Phospholipase Dα1 (PLDα1) and reactive oxygen species (ROS) are involved in many biotic or abiotic stress responses. Using the seedlings of Arabidopsis thaliana ecotype (WT), PLDα1 deficient mutant (pldα1) and the L-cysteine desulfhydrase (L-DEs) deficient mutant (lcd) as materials, the effect of H2S responding to osmotic stress and the functions of PLDα1 and ROS in this response were investigated. The results showed that H2S, PLDα1 and ROS were involved in osmotic stress resistance. Exogenous sodium hydrosulfide (NaHS) promoted the endogenous H2S content and up-regulated the expression of LCD in WT, lcd and plda1. Exogenous phosphatidic acid (PA) enhanced the H2S content and up-regulated the expressions of LCD in WT and plda1 but had no significant effect on the H2S content and LCD expression in lcd under osmotic stress. This suggested that H2S was located downstream of PLDα1 to participate in the osmotic stress signal response. Exogenous NaHS treatment regulated the antioxidant enzymes (SOD, POD, and CAT). The activities and the gene relative expressions of antioxidant enzymes in pldα1 and lcd were higher than those in WT under osmotic stress. This indicated that H2S and PLD regulated the antioxidant enzyme system under osmotic stress. The ROS level, electrolyte leakage (EL), malondialdehyde (MDA) were decreased by NaHS under osmotic stress, demonstrating H2S maintained the membrane integrity. All of these results revealed that H2S alleviated the osmotic stress by elevating PLD and suppressing ROS in A. thaliana.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Sulfeto de Hidrogênio/metabolismo , Pressão Osmótica , Fosfolipase D/fisiologia , Espécies Reativas de Oxigênio/metabolismo
20.
Arterioscler Thromb Vasc Biol ; 40(4): 874-884, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131614

RESUMO

Hydrogen sulfide has emerged as an important gaseous signaling molecule and a regulator of critical biological processes. However, the physiological significance of hydrogen sulfide metabolites such as persulfides, polysulfides, and other reactive sulfur species (RSS) has only recently been appreciated. Emerging evidence suggests that these RSS molecules may have similar or divergent regulatory roles compared with hydrogen sulfide in various biological activities. However, the chemical nature of persulfides and polysulfides is complex and remains poorly understood within cardiovascular and other pathophysiological conditions. Recent reports suggest that RSS can be produced endogenously, with different forms having unique chemical properties and biological implications involving diverse cellular responses such as protein biosynthesis, cell-cell barrier functions, and mitochondrial bioenergetics. Enzymes of the transsulfuration pathway, CBS (cystathionine beta-synthase) and CSE (cystathionine gamma-lyase), may also produce RSS metabolites besides hydrogen sulfide. Moreover, CARSs (cysteinyl-tRNA synthetase) are also able to generate protein persulfides via cysteine persulfide (CysSSH) incorporation into nascently formed polypeptides suggesting a new biologically relevant amino acid. This brief review discusses the biochemical nature and potential roles of RSS, associated oxidative stress redox signaling, and future research opportunities in cardiovascular disease.


Assuntos
Doenças Cardiovasculares/metabolismo , Sulfeto de Hidrogênio/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Disponibilidade Biológica , Doenças Cardiovasculares/fisiopatologia , Cistationina gama-Liase/genética , Humanos , Óxidos de Nitrogênio/metabolismo , Oxirredução , Polimorfismo Genético , Sulfetos/metabolismo , Remodelação Vascular
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