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1.
J Agric Food Chem ; 68(2): 503-511, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31869217

RESUMO

Due to nonuniform maturation, some plants may not be at the recommended stage of maturity when preharvest glyphosate is applied. The objective of this study was to determine how preharvest glyphosate timing affects wheat starch physicochemical properties. Two wheat cultivars were grown in three locations, and glyphosate was applied at the soft dough stage (early application) and the ripe stage (commercial standard). Upon harvest, starch chemical characteristics were studied. The proportion of B-type starch granules was lower in treated samples, although the starch molecular weight was not affected. Rapidly digestible starch content was highest when glyphosate was applied at the ripe stage, and lowest in the control, and vice versa for slowly digestible starch. Additionally, flour pasting viscosity was significantly higher in samples treated at the soft dough stage. Overall, the effects on wheat starch physicochemical characteristics were more pronounced when glyphosate was applied at the soft dough stage of maturity.


Assuntos
Glicina/análogos & derivados , Herbicidas/farmacologia , Amido/química , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Fenômenos Químicos , Glicina/farmacologia , Sementes/química , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Amido/metabolismo , Triticum/química , Triticum/metabolismo
2.
Food Chem ; 306: 125626, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31627083

RESUMO

The effect of glycine betaine (GB) on chilling injury (CI)-induced pericarp browning in 'Nanguo' pears was investigated during shelf life at 20 °C after storage at 0 °C for 120 d. GB treatment alleviated the severity of browning in 'Nanguo' pears as represented by lower browning index (BI) and browning incidence. Membrane lipid peroxidation in GB-treated fruit was lower than that in the control, and membrane integrity was maintained in good condition. The activities and expression of ascorbate peroxidase (APX), catalase (CAT), and superoxide dismutase (SOD) were higher in GB-treated fruit than in control fruit. Furthermore, significantly higher proline content, proline synthesis key enzyme activities, and gene expression were observed in the treated fruit, including ornithine d-aminotransferase (OAT) and Δ1-pyrroline-5-carbox-ylate synthetase (P5CS), which were consistent with the browning tendency. In a nutshell, GB treatment can effectively alleviate pericarp browning of cold-stored 'Nanguo' pears by regulating antioxidant enzymes and proline metabolism.


Assuntos
Betaína/farmacologia , Glicina/farmacologia , Pyrus/metabolismo , Antioxidantes/metabolismo , Catalase/metabolismo , Temperatura Baixa , Frutas/metabolismo , Peroxidase/metabolismo , Prolina/metabolismo , Pyrus/efeitos dos fármacos , Superóxido Dismutase/metabolismo
3.
J Agric Food Chem ; 67(47): 13010-13020, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31670946

RESUMO

Increasing the yield of soybean is a challenge to humankind dependent on several management practices, such as fertilizing and weed control. While glyphosate contributes to controlling weeds, it can interfere with spray mixture stability and, supposedly, complex with micronutrients within the plant tissue. This study investigated the effects of glyphosate on soybean foliar uptake and transport of Mn supplied as MnSO4, MnHPO3, Mn-ethylenediamine tetraacetic acid (EDTA), and MnCO3. These fertilizers induced ultrastructural changes in the leaf cuticle, regardless of the glyphosate mixture. Except for MnCO3, all tested sources increased the Mn content in the petiole. The mixture of glyphosate impaired Mn transport from MnSO4 and MnHPO3, but no evidence of Mn-glyphosate complexation within the plant was found. Manganese is rather transported in a similar chemical environment regardless of the source, except for Mn-EDTA, which was absorbed and transported in its pristine form. Interferences of glyphosate seem to be related to complexations in the tank mixture rather than affecting nutrients' metabolism.


Assuntos
Glicina/análogos & derivados , Herbicidas/farmacologia , Manganês/metabolismo , Folhas de Planta/química , Soja/efeitos dos fármacos , Soja/metabolismo , Transporte Biológico , Glicina/química , Glicina/farmacologia , Cinética , Manganês/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Soja/química , Espectrometria por Raios X
4.
Neurochem Res ; 44(11): 2658-2669, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612303

RESUMO

Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.


Assuntos
Glicina/farmacologia , MicroRNAs/fisiologia , Fármacos Neuroprotetores/farmacologia , PTEN Fosfo-Hidrolase/fisiologia , Transdução de Sinais/fisiologia , Hemorragia Subaracnóidea/fisiopatologia , Animais , Encéfalo/patologia , Linhagem Celular Tumoral , Humanos , Masculino , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologia
5.
Eur J Med Chem ; 182: 111646, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521028

RESUMO

The immunoproteasome, a specialized form of proteasome, is mainly expressed in lymphocytes and monocytes of jawed vertebrates and responsible for the generation of antigenic peptides for cell-mediated immunity. Overexpression of immunoproteasome have been detected in a wide range of diseases including malignancies, autoimmune and inflammatory diseases. Following the successful approval of constitutive proteasome inhibitors bortezomib, carfilzomib and Ixazomib, and with the clarification of immunoproteasome crystal structure and functions, a variety of immunoproteasome inhibitors were discovered or rationally developed. Not only the inhibitory activities, the selectivities for immunoproteasome over constitutive proteasome are essential for the clinical potential of these analogues, which has been validated by the clinical evaluation of immunoproteasome-selective inhibitor KZR-616 for the treatment of systemic lupus erythematosus. In this review, structure, function as well as the current developments of various inhibitors against immunoproteasome are going to be summarized, which help to fully understand the target for drug discovery.


Assuntos
Antineoplásicos/farmacologia , Doenças Autoimunes/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Animais , Antineoplásicos/química , Doenças Autoimunes/metabolismo , Compostos de Boro/química , Compostos de Boro/farmacologia , Bortezomib/química , Bortezomib/farmacologia , Glicina/análogos & derivados , Glicina/química , Glicina/farmacologia , Neoplasias Hematológicas/metabolismo , Humanos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Inibidores de Proteassoma/química
6.
Org Biomol Chem ; 17(37): 8618-8627, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31528932

RESUMO

A rational approach that may be applied to a broad class of enzyme-catalyzed reactions to design enzyme inhibitors affords a powerful strategy, facilitating the development of drugs and/or molecular probes of enzyme mechanisms. A strategy for the development of substrate-product analogues (SPAs) as inhibitors of racemases and epimerases is elaborated using isoleucine 2-epimerase from Lactobacillus buchneri (LbIleE) as a model enzyme. LbIleE catalyzes the PLP-dependent, reversible, racemization or epimerization of nonpolar amino acids at the C-2 position. The enzyme plays an important role in the biosynthesis of branched-chain d-amino acids and is a potential target for the development of antimicrobial agents. 3-Ethyl-3-methyl-l-norvaline (Ki = 2.9 ± 0.2 mM) and 3-ethyl-3-methyl-d-norvaline (Ki = 1.5 ± 0.2 mM) were designed as SPAs based on the movement of the sec-butyl side chain of the substrate l-Ile during catalysis, and were competitive inhibitors with binding affinities exceeding that of l-Ile by 1.3- and 2.5-fold, respectively. Surprisingly, these compounds were not substrates, but the corresponding compounds lacking the 3-methyl group were substrates. Unlike serine, glutamate, and proline racemases, which exhibit stringent steric requirements at their active sites, the active site of LbIleE was amenable to binding bulky SPAs. Moreover, LbIleE bound the SPA 2,2-di-n-butylglycine (Ki = 11.0 ± 0.2 mM) as a competitive inhibitor, indicating that the hydrophobic binding pocket at the active site was sufficiently plastic to tolerate gem-dialkyl substitution at the α-carbon of an amino acid. Overall, these results reveal that amino acid racemases/epimerases are amenable to inhibition by SPAs provided that they possess a capacious active site.


Assuntos
Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Glicina/farmacologia , Isoleucina/antagonistas & inibidores , Lactobacillus/enzimologia , Racemases e Epimerases/antagonistas & inibidores , Valina/análogos & derivados , Sítios de Ligação/efeitos dos fármacos , Biocatálise/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glicina/análogos & derivados , Glicina/química , Isoleucina/metabolismo , Modelos Moleculares , Conformação Molecular , Racemases e Epimerases/metabolismo , Especificidade por Substrato , Valina/síntese química , Valina/química , Valina/farmacologia
7.
J Environ Sci Health B ; 54(8): 681-692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403392

RESUMO

Although there are many reports on the dangers posed by glyphosate, this herbicide is still one of the most popular and widely used total weed killers. Therefore, great effort should be made to minimize exposure to this herbicide and limit its losses into the environment. The aim of this study was to prepare a new formulation consisted of various molecular weight chitosans with glyphosate and their evaluation toward active substance release, phytotoxicity, and preliminary herbicidal efficiency. The phytotoxicity study of the obtained chitosan/glyphosate formulations was determined based on the Organisation for Economic Co-operation and Development 208 guideline. Among all tested formulations evaluated for phytotoxicity, that containing the highest molecular weight of chitosan was found to be the least toxic, showing simultaneously the most effective herbicidal activity against selected weeds. The release rate of glyphosate from the obtained formulations was dependent on the molecular weight and viscosity of chitosan.


Assuntos
Quitosana/química , Glicina/análogos & derivados , Herbicidas/química , Herbicidas/farmacologia , Quitosana/farmacologia , Glicina/química , Glicina/farmacocinética , Glicina/farmacologia , Herbicidas/farmacocinética , Peso Molecular , Plantas Daninhas/efeitos dos fármacos
8.
J Agric Food Chem ; 67(36): 10010-10017, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414816

RESUMO

Dominican farmers have started to apply synthetic auxin herbicides (SAHs) as the main alternative to mitigate the impacts of the occurrence of glyphosate-resistant (GR) Parthenium hysterophorus populations in citrus orchards. A GR P. hysterophorus population survived field labeled rates of glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), dicamba, and picloram, which showed poor control (<50%). In in vivo assays, resistance levels were high for glyphosate and moderate for picloram, dicamba, and 2,4-D. Sequencing the 5-enolpyruvylshikimate-3-phosphate synthase gene revealed the double Thr-102-Ile and Pro-106-Ser amino acid substitution, conferring resistance to glyphosate. Additionally, reduced absorption and impaired translocation contributed to this resistance. Regarding SAH, impaired 2,4-D transport and enhanced metabolism were confirmed in resistant plants. The application of malathion improved the efficacy of SAHs (control >50%), showing that metabolism of these herbicides was mediated by cytochrome P450 enzymes. This study reports, for the first time, multiple resistance to SAHs and glyphosate in P. hysterophorus.


Assuntos
Asteraceae/efeitos dos fármacos , Citrus/crescimento & desenvolvimento , Glicina/análogos & derivados , Resistência a Herbicidas , Herbicidas/farmacologia , Ácidos Indolacéticos/farmacologia , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/farmacologia , Asteraceae/metabolismo , Dicamba/metabolismo , Dicamba/farmacologia , Glicina/metabolismo , Glicina/farmacologia , Herbicidas/metabolismo , Ácidos Indolacéticos/metabolismo
9.
Nat Commun ; 10(1): 3704, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420556

RESUMO

Herbicides increase crop yields by allowing weed control and harvest management. Glyphosate is the most widely-used herbicide active ingredient, with $11 billion spent annually on glyphosate-containing products applied to >350 million hectares worldwide, using about 8.6 billion kg of glyphosate. The herbicidal effectiveness of glyphosate can depend upon the time of day of spraying. Here, we show that the plant circadian clock regulates the effectiveness of glyphosate. We identify a daily and circadian rhythm in the inhibition of plant development by glyphosate, due to interaction between glyphosate activity, the circadian oscillator and potentially auxin signalling. We identify that the circadian clock controls the timing and extent of glyphosate-induced plant cell death. Furthermore, the clock controls a rhythm in the minimum effective dose of glyphosate. We propose the concept of agricultural chronotherapy, similar in principle to chronotherapy in medical practice. Our findings provide a platform to refine agrochemical use and development, conferring future economic and environmental benefits.


Assuntos
Morte Celular/efeitos dos fármacos , Relógios Circadianos/genética , Ritmo Circadiano/genética , Glicina/análogos & derivados , Resistência a Herbicidas/fisiologia , Herbicidas/farmacologia , Arabidopsis/efeitos dos fármacos , Cronoterapia , Ontologia Genética , Glicina/farmacologia , Hipocótilo , Ácidos Indolacéticos/metabolismo , Transdução de Sinais
10.
Mar Drugs ; 17(8)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416181

RESUMO

The objective of this research was to extract and prepare mycosporine-like amino acids (MAAs) and investigate the mechanism by which they act against UV-induced skin photoaging in Institute of Cancer Research (ICR ) mice. MAAs such as porphyra-334 and shinorine were extracted from Porphyra yezoensis, separated, and purified using column chromatography with SA-2 cation exchange resin. The effects of MAAs on the activity of endogenous antioxidant enzymes, namely total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were analyzed in mouse skin tissue. Pathological changes of skin tissue caused by ultraviolet radiation and the arrangement of collagen were observed by Hematoxylin-Eosin (HE) staining and scanning electron microscopy (SEM). Interleukin 1ß (IL-1ß), IL-6, and IL-10 were detected using the quantitative real-time reverse transcription-polymerase chain reaction (qPCR) and Enzyme Linked Immunosorbent Assay (ELISA). The concentration and expression of these proinflammatory cytokines was associated with the presence of nuclear factor (NF)-κB. The results show that MAA compounds from Porphyra yezoensis could suppress UV-induced photoaging of skin by inhibiting the reduction of endogenous antioxidant enzymes. Compared to the control group, the concentrations of SOD, GSH-Px, and CAT increased significantly in skin tissue homogenate following the external administration of MAAs (p < 0.05, p < 0.01), while the content of MDA decreased significantly (p < 0.05). Meanwhile, the administration of MAAs was associated with down-regulations in the concentration and mRNA expression of NF-κB, IL-1ß, IL-6, and IL-10. The results suggest that MAAs could protect skin from photodamage by increasing antioxidant enzyme activities and inhibiting inflammation.


Assuntos
Aminoácidos/farmacologia , Cicloexanonas/farmacologia , Cicloexilaminas/farmacologia , Glicina/análogos & derivados , Substâncias Protetoras/farmacologia , Dermatopatias/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Glicina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Dermatopatias/metabolismo
12.
Chemosphere ; 233: 905-912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340418

RESUMO

We investigated the interconnected roles of reactive oxygen species (ROS) generated upon seed exposure to glyphosate and/or gibberellic acid (GA3), and the possible interaction between the herbicide and the plant hormone during germination of sorghum seeds. GA3 decreased antioxidant enzyme activity in embryos, and the over accumulation of hydrogen peroxide (H2O2) in 1000 mM GA3-treated seeds resulted in the lowest germinability among treatments. The deleterious effects of glyphosate on germination rate, in contrast, were not related to H2O2 accumulation, but to its interference with the mitochondrial electron transport chain. However, interactions among glyphosate, GA3 and H2O2 during seed germination were observed. Similar to paclobutrazol, glyphosate appears to interfere with the de novo synthesis of gibberellin, which modulates seed germination through oxidative metabolism. Seeds experiencing increased oxidative status due to GA3 (100 mM) or H2O2 (50 mM) applications had the effects of glyphosate on germination rate reversed. Since decreased ATP synthesis is a secondary effect of glyphosate, increased H2O2 concentrations in embryos must facilitate germination by decreasing the energy required by ATP-demanding metabolism. Our results showed that glyphosate affect seed germination of sorghum, and that the herbicide interacts with oxidative and gibberellin metabolisms.


Assuntos
Germinação/efeitos dos fármacos , Giberelinas/metabolismo , Glicina/análogos & derivados , Herbicidas/farmacologia , Peróxido de Hidrogênio/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Sorghum/metabolismo , Antioxidantes/metabolismo , Grão Comestível/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Glicina/farmacologia , Sementes/efeitos dos fármacos
13.
Ann Hematol ; 98(9): 2063-2072, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312928

RESUMO

Rigosertib is a novel multi-kinase inhibitor, which has clinical activity towards leukemic progenitor cells of patients with high-risk myelodysplastic syndromes (MDS) after failure or progression on hypomethylating agents. Since the bone marrow microenvironment plays an important role in MDS pathogenesis, we investigated the impact of rigosertib on cellular compartments within the osteo-hematopoietic niche. Healthy C57BL/6J mice treated with rigosertib for 3 weeks showed a mild suppression of hematopoiesis (hemoglobin and red blood cells, both - 16%, p < 0.01; white blood cells, - 34%, p < 0.05; platelets, - 38%, p < 0.05), whereas there was no difference in the number of hematopoietic stem cells in the bone marrow. Trabecular bone mass of the spine was reduced by rigosertib (- 16%, p = 0.05). This was accompanied by a lower trabecular number and thickness (- 6% and - 10%, respectively, p < 0.05), partly explained by the increase in osteoclast number and surface (p < 0.01). Milder effects of rigosertib on bone mass were detected in an MDS mouse model system (NHD13). However, rigosertib did not further aggravate MDS-associated cytopenia in NHD13 mice. Finally, we tested the effects of rigosertib on human mesenchymal stromal cells (MSC) in vitro and demonstrated reduced cell viability at nanomolar concentrations. Deterioration of the hematopoietic supportive capacity of MDS-MSC after rigosertib pretreatment demonstrated by decreased number of colony-forming units, especially in the monocytic lineage, further supports the idea of disturbed crosstalk within the osteo-hematopoietic niche mediated by rigosertib. Thus, rigosertib exerts inhibitory effects on the stromal components of the osteo-hematopoietic niche which may explain the dissociation between anti-leukemic activity and the absence of hematological improvement.


Assuntos
Glicina/análogos & derivados , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Síndromes Mielodisplásicas , Nicho de Células-Tronco/efeitos dos fármacos , Sulfonas/farmacologia , Animais , Glicina/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Transgênicos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia
14.
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
15.
Int Immunopharmacol ; 73: 312-320, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31129418

RESUMO

Progressive lung injury and pulmonary inflammation can be induced by an intraperitoneal injection of lipopolysaccharide (LPS). Interleukin-1ß (IL-1ß) is a key pro-inflammatory cytokine that can further exaggerate inflammation, which is cleaved and activated by the NALP3 inflammasome. Although the nuclear receptor Rev-erbα attenuates the level of LPS-induced pulmonary inflammation, the mechanism remains unclear. In this study, we investigated the influence of LPS-induced production of IL-1ß and Rev-erbα on the development of lung inflammation. Herein, we demonstrate that Rev-erbα reduces IL-1ß production and lung injury following an intraperitoneal injection of LPS, which is dependent on the NF-κB/NALP3 pathway. Thus, Rev-erbα is able to decrease the extent of acute lung injury by regulating IL-1ß production. This mechanism may represent a potential novel therapeutic approach for lung injury.


Assuntos
Lesão Pulmonar Aguda/imunologia , NF-kappa B/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/imunologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Glicina/análogos & derivados , Glicina/farmacologia , Interleucina-1beta/imunologia , Isoquinolinas/farmacologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/agonistas , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Células RAW 264.7 , Transdução de Sinais , Tiofenos/farmacologia
16.
Cell Biochem Biophys ; 77(3): 261-272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31065867

RESUMO

Our early studies have shown that sodium thiosulfate (STS) treatment attenuated the ischemia-reperfusion (IR)-induced injury in an isolated rat heart model by decreasing apoptosis, oxidative stress, and preserving mitochondrial function. Hydrogen sulfide, the precursor molecule is reported to have similar efficacy. This study aims to investigate the role of endogenous hydrogen sulfide in STS-mediated cardioprotection against IR in an isolated rat heart model. D, L-propargylglycine (PAG), an inhibitor of cystathionine γ-lyase was used as endogenous H2S blocker. In addition, we used the hypoxia-reoxygenation (HR) model to study the impact of STS in cardiomyocytes (H9C2) and fibroblast (3T3) cells. STS treatment to animal and cells prior to IR or HR decreased cell injury. The sensitivity of H9C2 and 3T3 cells towards HR (6 h hypoxia followed by 12 h reoxygenation) challenge varies, where, 3T3 cells exhibited higher cell death (54%). Cells treated with PAG prior to STS abrogate the protective effect in 3T3 (cell viability 61%) but not in H9C2 (cell viability 82%). Further evaluation in rat heart model showed partial recovery (46% RPP) of heart from those hearts pretreated with PAG prior to STS condition. In conclusion, we demonstrated that STS-mediated cardioprotection to IR-challenged rat heart is not fully dependent on endogenous H2S level and this dependency may be linked to higher fibroblast content in rat heart.


Assuntos
Antídotos/farmacologia , Apoptose/efeitos dos fármacos , Cistationina gama-Liase/metabolismo , Miocárdio/enzimologia , Tiossulfatos/farmacologia , Alquinos/farmacologia , Animais , Antídotos/uso terapêutico , Antioxidantes/química , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cistationina gama-Liase/antagonistas & inibidores , Glicina/análogos & derivados , Glicina/farmacologia , Coração/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos , Ratos Wistar , Tiossulfatos/uso terapêutico
17.
J Agric Food Chem ; 67(22): 6133-6142, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31067046

RESUMO

Glyphosate-based herbicide (GBH) applications were reported to induce physiological damages to glyphosate-resistant (GR) soybean, which were mainly attributed to aminomethylphosphonic acid (AMPA). In order to study glyphosate and AMPA dynamics in plants and associated phytotoxic effects, a greenhouse experiment was set where GR soybeans were exposed to GBH (0.7 to 4.5 kg glyphosate ha-1) and sampled over time (2, 7, 14, and 28 days after treatment (DAT)). Hydrogen peroxide content increased 2 DAT, while a decrease was observed for the effective quantum yield (2, 7, 14 DAT), stomatal conductance (2 DAT), and biomass (14 DAT). Glyphosate content was higher in leaves, followed by stems, and then roots. AMPA content tended to increase with time, especially in roots, and the amount of AMPA in roots was negatively correlated to mostly all phytotoxicity indicators. This finding is important since AMPA residues are measured in agricultural soils several months after GBH applications, which could impact productivity in GR crops.


Assuntos
Glicina/análogos & derivados , Resistência a Herbicidas , Herbicidas/análise , Compostos Organofosforados/análise , Soja/química , Glicina/análise , Glicina/metabolismo , Glicina/farmacologia , Herbicidas/metabolismo , Herbicidas/farmacologia , Compostos Organofosforados/metabolismo , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Caules de Planta/química , Caules de Planta/efeitos dos fármacos , Caules de Planta/metabolismo , Soja/efeitos dos fármacos , Soja/metabolismo
18.
Nutrients ; 11(5)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083508

RESUMO

Glutathione (GSH) is a critical endogenous antioxidant found in all eukaryotic cells. Higher GSH concentrations protect against cellular damage, tissue degeneration, and disease progression in various models, so there is considerable interest in developing interventions that augment GSH biosynthesis. Oral GSH supplementation is not the most efficient option due to the enzymatic degradation of ingested GSH within the intestine by γ-glutamyltransferase, but supplementation of its component amino acids-cysteine, glycine, and glutamate-enhances tissue GSH synthesis. Furthermore, supplementation with some non-precursor amino acids and micronutrients appears to influence the redox status of GSH and related antioxidants, such as vitamins C and E, lowering systemic oxidative stress and slowing the rate of tissue deterioration. In this review, the effects of oral supplementation of amino acids and micronutrients on GSH metabolism are evaluated. And since specific dietary patterns and diets are being prescribed as first-line therapeutics for conditions such as hypertension and diabetes, the impact of overall diets on GSH homeostasis is also assessed.


Assuntos
Aminoácidos/farmacologia , Antioxidantes/metabolismo , Dieta , Suplementos Nutricionais , Glutationa/metabolismo , Micronutrientes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Ácido Ascórbico/metabolismo , Cisteína/farmacologia , Ácido Glutâmico/farmacologia , Glicina/farmacologia , Homeostase , Humanos , Vitamina E/metabolismo
19.
Arch Microbiol ; 201(8): 1029-1045, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31111187

RESUMO

Endophytic bacteria isolated from non-transgenic and transgenic Roundup Ready® glyphosate-resistant (GR) soybean plants were investigated to analyze the correspondence between phenotypic and genotypic characteristics and to determine whether or not the strains could be grouped based on the source of isolation in transgenic or non-transgenic plants, respectively. Most of the strains recovered from GR plants have shown the ability for plant growth promotion (PGP) by means of IAA production and inorganic phosphate solubilization, and 100% of the strains showed great motility (swarm or swim); in addition, 90% of the strains were able to metabolize the majority of carbon sources tested. GR soybean fields showed higher endophytes abundance than non-transgenic; however, analyzing the phylogenetic trees constructed using the partial 16SrRNA gene sequences, higher diversity was observed in non-transgenic soybean fields. Overall the majority of isolated endophytes could utilize multiple patterns of carbon sources and express resistance to antibiotics, while isolates varied widely in the PGP ability. The greater pattern and frequency of utilization of carbon sources and frequency and intensity of antibiotic resistance compared with PGP ability within the soybean endophytes community suggest that carbon sources metabolism and antibiotic resistance confer a greater relative fitness benefit than PGP ability. In conclusion, cluster analysis of the phenotypes and 16SrRNA gene sequences reveals lack of correspondence between the pattern of bacterial isolates and the transgenic character of plants, and the heterogeneity of clustering suggested that various adaptive processes, such as stress response, could have contributed to generate phenotypic variability to enhance endophytes overall fitness.


Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Endófitos/classificação , Endófitos/isolamento & purificação , Soja/genética , Bactérias/genética , Endófitos/genética , Genótipo , Glicina/análogos & derivados , Glicina/farmacologia , Resistência a Herbicidas/genética , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Soja/efeitos dos fármacos , Soja/microbiologia
20.
Int J Mol Sci ; 20(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096560

RESUMO

The introduction of glyphosate-resistant (GR) crops revolutionized weed management; however, the improper use of this technology has selected for a wide range of weeds resistant to glyphosate, referred to as superweeds. We characterized the high glyphosate resistance level of an Amaranthus hybridus population (GRH)-a superweed collected in a GR-soybean field from Cordoba, Argentina-as well as the resistance mechanisms that govern it in comparison to a susceptible population (GSH). The GRH population was 100.6 times more resistant than the GSH population. Reduced absorption and metabolism of glyphosate, as well as gene duplication of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) or its overexpression did not contribute to this resistance. However, GSH plants translocated at least 10% more 14C-glyphosate to the rest of the plant and roots than GRH plants at 9 h after treatment. In addition, a novel triple amino acid substitution from TAP (wild type, GSH) to IVS (triple mutant, GRH) was identified in the EPSPS gene of the GRH. The nucleotide substitutions consisted of ATA102, GTC103 and TCA106 instead of ACA102, GCG103, and CCA106, respectively. The hydrogen bond distances between Gly-101 and Arg-105 positions increased from 2.89 Å (wild type) to 2.93 Å (triple-mutant) according to the EPSPS structural modeling. These results support that the high level of glyphosate resistance of the GRH A. hybridus population was mainly governed by the triple mutation TAP-IVS found of the EPSPS target site, but the impaired translocation of herbicide also contributed in this resistance.


Assuntos
3-Fosfoshikimato 1-Carboxiviniltransferase/genética , Amaranthus/efeitos dos fármacos , Amaranthus/genética , Substituição de Aminoácidos , Glicina/análogos & derivados , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Argentina , Relação Dose-Resposta a Droga , Duplicação Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glicina/metabolismo , Glicina/farmacologia , Mutação/efeitos dos fármacos , Fosfatos/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/genética , Alinhamento de Sequência , Análise de Sequência de Proteína , Ácido Chiquímico/metabolismo , Soja
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