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1.
Ecotoxicol Environ Saf ; 221: 112437, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34153540

RESUMO

Agricultural soils are receiving higher inputs of trace elements (TEs) from anthropogenic activities. Application of nanoparticles (NPs) in agriculture as nano-pesticides and nano-fertilizers has gained rapid momentum worldwide. The NPs-based fertilizers can facilitate controlled-release of nutrients which may be absorbed by plants more efficiently than conventional fertilizers. Due to their large surface area with high sorption capacity, NPs can be used to reduce excess TEs uptake by plants. The present review summarizes the effects of NPs on plant growth, photosynthesis, mineral nutrients uptake and TEs concentrations. It also highlights the possible mechanisms underlying NPs-mediated reduction of TEs toxicity at the soil and plant interphase. Nanoparticles are effective in immobilization of TEs in soil through alteration of their speciation and improving soil physical, chemical, and biological properties. At the plant level, NPs reduce TEs translocation from roots to shoots by promoting structural alterations, modifying gene expression, and improving antioxidant defense systems. However, the mechanisms underlying NPs-mediated TEs uptake and toxicity reduction vary with NPs type, mode of application, time of NPs exposure, and plant conditions (e.g., species, cultivars, and growth rate). The review emphasizes that NPs may provide new perspectives to resolve the problem of TEs toxicity in crop plants which may also reduce the food security risks. However, the potential of NPs in metal-contaminated soils is only just starting to be realized, and additional studies are required to explore the mechanisms of NPs-mediated TEs immobilization in soil and uptake by plants. Such future knowledge gap has been highlighted and discussed.


Assuntos
Nanopartículas , Plantas/efeitos dos fármacos , Oligoelementos/metabolismo , Oligoelementos/toxicidade , Agricultura , Metais/metabolismo , Metais/toxicidade , Raízes de Plantas/metabolismo , Plantas/metabolismo , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade
2.
Nat Commun ; 12(1): 3867, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162839

RESUMO

Enzymes can evolve new catalytic activity when environmental changes present them with novel substrates. Despite this seemingly straightforward relationship, factors other than the direct catalytic target can also impact adaptation. Here, we characterize the catalytic activity of a recently evolved bacterial methyl-parathion hydrolase for all possible combinations of the five functionally relevant mutations under eight different laboratory conditions (in which an alternative divalent metal is supplemented). The resultant adaptive landscapes across this historical evolutionary transition vary in terms of both the number of "fitness peaks" as well as the genotype(s) at which they are found as a result of genotype-by-environment interactions and environment-dependent epistasis. This suggests that adaptive landscapes may be fluid and molecular adaptation is highly contingent not only on obvious factors (such as catalytic targets), but also on less obvious secondary environmental factors that can direct it towards distinct outcomes.


Assuntos
Adaptação Fisiológica/genética , Bactérias/genética , Proteínas de Bactérias/genética , Epistasia Genética , Hidrolases/genética , Sequência de Aminoácidos , Bactérias/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Biocatálise , Evolução Molecular , Interação Gene-Ambiente , Genótipo , Hidrolases/química , Hidrolases/metabolismo , Cinética , Metais/química , Metais/metabolismo , Metil Paration/química , Metil Paration/metabolismo , Mutação , Domínios Proteicos , Homologia de Sequência de Aminoácidos
3.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070465

RESUMO

Environmental or abiotic stresses are a common threat that remains a constant and common challenge to all plants. These threats whether singular or in combination can have devastating effects on plants. As a semiaquatic plant, rice succumbs to the same threats. Here we systematically look into the involvement of salicylic acid (SA) in the regulation of abiotic stress in rice. Studies have shown that the level of endogenous salicylic acid (SA) is high in rice compared to any other plant species. The reason behind this elevated level and the contribution of this molecule towards abiotic stress management and other underlying mechanisms remains poorly understood in rice. In this review we will address various abiotic stresses that affect the biochemistry and physiology of rice and the role played by SA in its regulation. Further, this review will elucidate the potential mechanisms that control SA-mediated stress tolerance in rice, leading to future prospects and direction for investigation.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Oryza/metabolismo , Ácido Salicílico/metabolismo , Estresse Fisiológico/fisiologia , Resposta ao Choque Frio/fisiologia , Secas , Regulação da Expressão Gênica de Plantas/genética , Resposta ao Choque Térmico/fisiologia , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Metais/metabolismo , Metais/toxicidade , Oryza/enzimologia , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Salino/fisiologia
4.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072023

RESUMO

This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the MT1A (rs11640851), MT1B (rs964372) and MT2A (rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the MT1B gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the MT1A gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the MT1A gene by more than fourfold. The investigated polymorphisms, rs11640851 in the MT1A gene, rs964372 in the MT1B gene and rs10636 in the MT2A gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.


Assuntos
Suscetibilidade a Doenças , Metalotioneína/genética , Metais/efeitos adversos , Pancreatite/etiologia , Polimorfismo de Nucleotídeo Único , Fumantes , Alelos , Antioxidantes/metabolismo , Biomarcadores , Predisposição Genética para Doença , Genótipo , Homeostase , Humanos , Mediadores da Inflamação/metabolismo , Metais/metabolismo , Razão de Chances
5.
Plant Cell Rep ; 40(7): 1199-1213, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33983490

RESUMO

KEY MESSAGE: Bacillus spizizenii is for the first time described as a plant growth salt-tolerant bacterium able to alleviate salt stress in crop plants by improving physiological parameters and antioxidant defense mechanisms. Agricultural soil salinization is a serious issue worldwide affecting agricultural yield. Plant growth promoting bacteria can enhance salt tolerance and plant yield. Bacillus spizizenii FMH45 has been shown to inhibit fungal attacks in tomato fruits and to augment tomato seed germination in presence of abiotic stresses. During this study, we reported for the first time B. spizizenii as a salt-tolerant bacterium able to alleviate salt stress in tomato plants. B. spizizenii FMH45 was examined in vitro for its potential to produce several plant growth promoting characters (siderophores, IAA, and phosphate solubilization) and hydrolytic enzymes (cellulase, glucanase and protease) in the presence of saline conditions. FMH45 was also investigated in vivo in pot experiments to evaluate its ability to promote tomato plant growth under salt stress condition. FMH45 inoculation, enhanced tomato seedling length, vigor index, and plant fresh and dry weights when compared to the non-inoculated controls exposed and not exposed to a regular irrigation with salt solutions containing: 0; 3.5; 7; and 10 g L-1 of NaCl. FMH45-treated plants also presented improved chlorophyll content, membrane integrity (MI), and phenol peroxidase (POX) concentrations, as well as reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels under saline conditions with a significant salinity × strain interaction. Furthermore, FMH45 inoculation significantly decreased endogenous Na+ accumulation, increased K+ and Ca2+ uptake, and thereby improved K+/Na+ and Ca2+/Na+ ratios. This study proves that bio-inoculation of FMH45 efficiently increases salt tolerance in tomato plants. This sustainable approach can be applied to other stressed plant species in affected soils.


Assuntos
Inoculantes Agrícolas/fisiologia , Bacillus/fisiologia , Lycopersicon esculentum/fisiologia , Estresse Salino/fisiologia , Antioxidantes/metabolismo , Carotenoides/metabolismo , Membrana Celular/metabolismo , Clorofila/metabolismo , Germinação , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Metais/metabolismo , Peroxidase/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plântula/crescimento & desenvolvimento
6.
Aquat Toxicol ; 236: 105845, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33984608

RESUMO

Greater interest in commercial deep-sea mining has been accompanied by mounting environmental concerns, including metal contamination resulting from mining activities. However, little is known about the toxic effects of metal exposure on deep-sea life. Given its ability to accumulate metals from the surrounding environment, its wide distribution at both vents and seeps, and its high abundance, the deep-sea mussel Bathymodiolus platifrons could serve as an ideal model to investigate the toxicological responses of deep-sea organisms to metal exposure. Here, we evaluated metal accumulation, traditional metal-related biomarkers, namely acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase, catalase, reduced glutathione, metallothioneins, and malondialdehyde, as well as metabolic profiles in the gills of B. platifrons after a 7-day exposure to copper (100 µg/L), cadmium (500 µg/L), or copper-plus-cadmium treatments (100 µg/L Cu and 500 µg/L Cd). Metal exposure concentrations selected in this study can be found in deep-sea hydrothermal environments. Metal exposure resulted in significant metal accumulation in the gills of the mussel, indicating that B. platifrons has promise for use as an indicator of deep-sea metal pollution levels. Traditional biomarkers (AKP, ACP, and measured antioxidants) revealed cellular injury and oxidative stress in mussels following metal exposure. Metabolic responses in the three treatment groups indicated that metal exposure perturbed osmoregulation, energy metabolism, and nucleotide metabolism in mussels, in a response marked by differentially altered levels of amino acids, hypotaurine, betaine, succinate, glucose 6-phosphate, fructose 6-phosphate, guanosine, guanosine 5'-monophosphate, and inosine. Nevertheless, several uniquely altered metabolites were found in each treatment exposure group, suggesting dissimilar modes of toxicity between the two metal types. In the Cd-exposed group, the monosaccharide D-allose, which is involved in suppressing mitochondrial ROS production, was downregulated, a response consistent with oxidative stress in Cd-exposed B. platifrons. In the Cu-exposed group, the detected alterations in dopamine, dopamine-related, and serotonin-related metabolites together suggest disturbed neurotransmission in Cu-exposed B. platifrons. In the Cu-plus-Cd group, we detected a decline in fatty acid levels, implying that exposure to both metals jointly exerted a negative influence on the physiological functioning of the mussel. To the best of our knowledge, this is the first study to investigate changes in metabolite profiles in Bathymodiolus mussels exposed to metal. The findings reported here advance our understanding of the adverse impact of metal exposure on deep-sea life and can inform deep-sea mining assessments through the use of multiple biomarkers.


Assuntos
Cádmio/toxicidade , Cobre/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Brânquias/efeitos dos fármacos , Metalotioneína/metabolismo , Metais/metabolismo , Mineração , Mytilidae/efeitos dos fármacos , Estresse Oxidativo , Alimentos Marinhos , Superóxido Dismutase/metabolismo
7.
Food Chem ; 361: 130025, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029908

RESUMO

The relative concentration of available inorganic elements is critical for yeast growth and metabolism and has potential to be a tool leading to directed yeast flavour formation during fermentation. This study investigates the influence of essential inorganic elements during alcoholic fermentation of brewers wort, fermented using three independent yeast strains, Saccharomyces pastorianus W34/70, and Saccharomyces cerevisiae strains M2 and NCYC2592 under a range of conditions replicated for each yeast strain. 10 treatments were applied: 1 control and 9 inorganic supplementations: standard brewers wort, ammonia-nitrogen, inorganic phosphate, potassium, magnesium, copper, zinc, iron, manganese and a composite mixture, Twenty-five chemical markers were evaluated by HPLC (ethanol, glycerol), and GC-MS (aroma). There was a significant change in volatile aroma compounds during fermentation, which was more prominent when supplemented with ammonia nitrogen, inorganic phosphate, potassium or magnesium (P < 0.05). Heavy metal ions mostly had a negative effect on the flavour formation.


Assuntos
Cerveja/microbiologia , Metais/farmacologia , Saccharomyces/metabolismo , Cerveja/análise , Cromatografia Líquida de Alta Pressão , Etanol/metabolismo , Fermentação/efeitos dos fármacos , Microbiologia de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Glicerol/metabolismo , Metais/metabolismo , Odorantes , Potássio/metabolismo , Potássio/farmacologia , Saccharomyces/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo
8.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: covidwho-1136500

RESUMO

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.


Assuntos
Antivirais/química , Metais/química , Metisazona/química , Simulação de Acoplamento Molecular , SARS-CoV-2/química , Antivirais/metabolismo , COVID-19/tratamento farmacológico , Cálcio/química , Cálcio/metabolismo , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/química , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Desenho de Fármacos , Humanos , Ferro/química , Ferro/metabolismo , Magnésio/química , Magnésio/metabolismo , Manganês/química , Manganês/metabolismo , Metais/metabolismo , Metisazona/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Zinco/química , Zinco/metabolismo
9.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925312

RESUMO

Red cabbage (RC) and purple sweet potato (PSP) are naturally rich in acylated cyanidin glycosides that can bind metal ions and develop intramolecular π-stacking interactions between the cyanidin chromophore and the phenolic acyl residues. In this work, a large set of RC and PSP anthocyanins was investigated for its coloring properties in the presence of iron and aluminum ions. Although relatively modest, the structural differences between RC and PSP anthocyanins, i.e., the acylation site at the external glucose of the sophorosyl moiety (C2-OH for RC vs. C6-OH for PSP) and the presence of coordinating acyl groups (caffeoyl) in PSP anthocyanins only, made a large difference in the color expressed by their metal complexes. For instance, the Al3+-induced bathochromic shifts for RC anthocyanins reached ca. 50 nm at pH 6 and pH 7, vs. at best ca. 20 nm for PSP anthocyanins. With Fe2+ (quickly oxidized to Fe3+ in the complexes), the bathochromic shifts for RC anthocyanins were higher, i.e., up to ca. 90 nm at pH 7 and 110 nm at pH 5.7. A kinetic analysis at different metal/ligand molar ratios combined with an investigation by high-resolution mass spectrometry suggested the formation of metal-anthocyanin complexes of 1:1, 1:2, and 1:3 stoichiometries. Contrary to predictions based on steric hindrance, acylation by noncoordinating acyl residues favored metal binding and resulted in complexes having much higher molar absorption coefficients. Moreover, the competition between metal binding and water addition to the free ligands (leading to colorless forms) was less severe, although very dependent on the acylation site(s). Overall, anthocyanins from purple sweet potato, and even more from red cabbage, have a strong potential for development as food colorants expressing red to blue hues depending on pH and metal ion.


Assuntos
Antocianinas/química , Brassica/química , Ipomoea batatas/química , Pigmentos Biológicos/química , Acilação , Alumínio/química , Alumínio/metabolismo , Antocianinas/metabolismo , Brassica/metabolismo , Quelantes/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cor , Corantes de Alimentos , Concentração de Íons de Hidrogênio , Íons/metabolismo , Ipomoea batatas/metabolismo , Ferro/química , Ferro/metabolismo , Cinética , Metais/metabolismo , Fenóis/metabolismo , Extratos Vegetais/química
10.
Nucleic Acids Res ; 49(9): 5265-5277, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33885787

RESUMO

Since its initial characterization, Escherichia coli RNase I has been described as a single-strand specific RNA endonuclease that cleaves its substrate in a largely sequence independent manner. Here, we describe a strong calcium (Ca2+)-dependent activity of RNase I on double-stranded RNA (dsRNA), and a Ca2+-dependent novel hybridase activity, digesting the RNA strand in a DNA:RNA hybrid. Surprisingly, Ca2+ does not affect the activity of RNase I on single stranded RNA (ssRNA), suggesting a specific role for Ca2+ in the modulation of RNase I activity. Mutation of a previously overlooked Ca2+ binding site on RNase I resulted in a gain-of-function enzyme that is highly active on dsRNA and could no longer be stimulated by the metal. In summary, our data imply that native RNase I contains a bound Ca2+, allowing it to target both single- and double-stranded RNAs, thus having a broader substrate specificity than originally proposed for this traditional enzyme. In addition, the finding that the dsRNase activity, and not the ssRNase activity, is associated with the Ca2+-dependency of RNase I may be useful as a tool in applied molecular biology.


Assuntos
Cálcio/metabolismo , Endorribonucleases/metabolismo , RNA de Cadeia Dupla/metabolismo , Substituição de Aminoácidos , DNA , Endorribonucleases/química , Endorribonucleases/genética , Metais/metabolismo , RNA/metabolismo , Ribonucleases/metabolismo , Especificidade por Substrato
11.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804129

RESUMO

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.


Assuntos
Antivirais/química , Metais/química , Metisazona/química , Simulação de Acoplamento Molecular , SARS-CoV-2/química , Antivirais/metabolismo , COVID-19/tratamento farmacológico , Cálcio/química , Cálcio/metabolismo , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/química , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Desenho de Fármacos , Humanos , Ferro/química , Ferro/metabolismo , Magnésio/química , Magnésio/metabolismo , Manganês/química , Manganês/metabolismo , Metais/metabolismo , Metisazona/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Zinco/química , Zinco/metabolismo
12.
Arch Microbiol ; 203(5): 2615-2623, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33704545

RESUMO

Acidithiobacillus ferrooxidans (At. ferrooxidans) is a bacterium that has the ability to metabolize iron. It converts Fe2+ into Fe3+ during its metabolic cycle. Hence, the At. ferrooxidans spent medium is rich in Fe3+. The presence of Fe3+ contributes to a peroxidase-like activity. Therefore, in this study, an attempt has been made to explore the peroxidase-like activity of the At. ferrooxidans spent medium. It has been observed that the At. ferrooxidans spent medium oxidized 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). The effect of various process parameters on the peroxidase-like activity has been studied. Optimum peroxidase-like activity is achieved using 5 µl of the spent medium, 0.3 mM TMB concentration, 4 mM H2O2 concentration, 4.2 pH, and 40 °C temperature. The peroxidase-like activity of the At. ferrooxidans spent medium has been used to develop a colorimetric assay for detection of glutathione (GSH). GSH inhibits the peroxidase-like activity of the At. ferrooxidans spent medium in a concentration range of 0-1 mM. The limit of detection (LOD) of GSH, obtained using the calibration plot is 0.69 mM. The developed assay is selective toward GSH, as the presence of amino acids, metals, and sugars have shown a negligible effect on the GSH sensing ability.


Assuntos
Acidithiobacillus/metabolismo , Meios de Cultura/química , Glutationa/análise , Peroxidases/metabolismo , Benzidinas/metabolismo , Colorimetria , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Ferro/metabolismo , Metais/metabolismo , Oxirredução
13.
Biomed Pharmacother ; 137: 111396, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761612

RESUMO

The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary factors, including single-nucleotide polymorphisms (SNPs) of genes for coding insulin, insulin receptors, or insulin receptor substrates (INS, INSR, IRS1, IRS2) or superoxide dismutase isozymes (SOD1, SOD2, SOD3), have been linked with the incidence of obesity and diabetes. However, the underlying changes in the plasma concentration/activity of superoxide dismutase isozymes and their potential connection with the said hereditary factors remain unexplored. Previously, we have observed that the plasma concentration/activity of superoxide dismutase isozymes differs in the context of obesity and/or rs2234694 (SOD1) and rs4880 (SOD2) and that the concentrations of SOD1, SOD2, SOD3 are correlated with each other. Intersexual variability of SOD1 concentration was detected regardless of obesity. In this study, the variability of concentration/activity of superoxide dismutase isozymes in plasma is considered in the context of type 2 diabetes and/or SNPs: rs2234694 (SOD1), rs5746105 (SOD2), rs4880 (SOD2), rs927450 (SOD2), rs8192287 (SOD3). Genotypic variability of SNP rs3842729 (INS), previously studied in the context of insulin-dependent diabetes, is investigated in terms of selected clinical parameters associated with type 2 diabetes. This study revealed higher SOD1 concentration in diabetic men compared to women, and extremely high SOD1 concentration, higher total superoxide dismutase, and copper-zinc superoxide dismutase activity, and lower superoxide dismutase and copper-zinc superoxide dismutase activity (when adjusted for the concentration of SODs) in the diabetic group regardless of sex. Multiple logistic regression, applied to explore possible links between the studied SNPs and other factors with the odds of type 2 diabetes or obesity, revealed that the genotypic variability of rs4880 (SOD2) could affect these odds, supporting the findings of several other studies.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/genética , Insulina/genética , Polimorfismo de Nucleotídeo Único/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Adulto , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Metais/metabolismo , Pessoa de Meia-Idade , Obesidade/genética , Caracteres Sexuais , Fumar/metabolismo , Superóxido Dismutase-1/genética
14.
Biochimie ; 185: 53-67, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33727137

RESUMO

Inteins are intervening polypeptides that interrupt the functional domains of several important proteins across the three domains of life. Inteins excise themselves from the precursor protein, ligating concomitant extein residues in a process called protein splicing. Post-translational auto-removal of inteins remain critical for the generation of active proteins. The perspective of inteins in science is a robust field of research, however fundamental studies centralized upon splicing regulatory mechanism are imperative for addressing more intricate issues. Controlled engineering of intein splicing has many applications; intein inhibition can facilitate novel drug design, while activation of intein splicing is exploited in protein purification. This paper provides a comprehensive review of the past and recent advances in the splicing regulation via metal-intein interaction. We compare the behavior of different metal ions on diverse intein systems. Though metals such as Zn, Cu, Pt, Cd, Co, Ni exhibit intein inhibitory effect heterogeneously on different inteins, divalent metal ions such as Ca and Mg fail to do so. The observed diversity in the metal-intein interaction arises mostly due to intein polymorphism and variations in atomic structure of metals. A mechanistic understanding of intein regulation by metals in native as well as synthetically engineered intein systems may yield potent intein inhibitors via direct or indirect approach.


Assuntos
Inteínas , Metais/química , Processamento de Proteína , Metais/metabolismo
15.
Ecotoxicol Environ Saf ; 215: 112147, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33756294

RESUMO

The intensive shift on land cover by anthropogenic activities have led to changes in natural habitats and environmental contamination, which can ultimately impact and threat biodiversity and ecosystem services, such as pollination. The aim of this study was to evaluate the effect of native forest and human-modified land covers on the concentrations of chemical elements accumulated in the neotropical pollinator bee T. angustula. Eight landscapes, within an Ecological Corridor in the State of São Paulo, Brazil, with gradients of forest cover, spatial heterogeneity and varying land covers were used as sampling unities. Bees collected in traps or through actives searches had the concentration of 21 chemical elements determined by ICP-MS. Results show a beneficial effect of forested areas on the concentrations of some well-known toxic elements accumulated in bees, such as Hg, Cd, and Cr. Multivariate Redundancy Analysis (RDA) suggests road as the most important driver for the levels of Cr, Hg, Sb, Al, U, As, Pb and Pt and bare soil, pasture and urban areas as the landscape covers responsible for the concentrations of Zn, Cd, Mn, Mg, Ba and Sr in bees. The results reinforce the potential use of T. angustula bees as bioindicators of environmental quality and also show that these organisms are being directly affected by human land use, offering potential risks for the Neotropical ecosystem. Our study sheds light on how land covers (native forest and human-modified) can influence the levels of contaminants in insects within human-dominated landscapes. The generation of predictions of the levels of toxic metals and metalloids based on land use can both contribute to friendly farming planning as well as to support public policy development on the surrounding of protected areas and biodiversity conservation hotspots.


Assuntos
Abelhas/fisiologia , Monitoramento Ambiental , Metaloides/metabolismo , Metais/metabolismo , Agricultura , Animais , Biodiversidade , Brasil , Ecossistema , Florestas , Intoxicação por Metais Pesados , Humanos , Polinização , Solo
16.
Eur J Med Chem ; 216: 113310, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667847

RESUMO

A novel series of dimethylamino chalcone-O-alkylamines derivatives was designed and synthesized as multifunctional agents for the treatment of AD. All the target compounds exhibited significant abilities to inhibit and disaggregate Aß aggregation, and acted as potential selective AChE inhibitors, biometal chelators and selective MAO-B inhibitors. Among these compounds, compound TM-6 showed the greatest inhibitory activity against self-induced Aß aggregation (IC50 = 0.88 µM) and well disaggregation ability toward self-induced Aß aggregation (95.1%, 25 µM), the TEM images, molecular docking study and molecular dynamics simulations provided reasonable explanation for its high efficiency, and it was also found to be a remarkable antioxidant (ORAC-FL values of 2.1eq.), the best AChE inhibitor (IC50 = 0.13 µM) and MAO-B inhibitor (IC50 = 1.0 µM), as well as a good neuroprotectant. UV-visual spectrometry and ThT fluorescence assay revealed that compound TM-6 was not only a good biometal chelator by inhibiting Cu2+-induced Aß aggregation (95.3%, 25 µM) but also could disassemble the well-structured Aß fibrils (88.1%, 25 µM). Further, TM-6 could cross the blood-brain barrier (BBB) in vitro. More importantly, compound TM-6 did not show any acute toxicity in mice at doses of up to 1000 mg/kg and improved scopolamine-induced memory impairment. Taken together, these data indicated that TM-6, an excellent balanced multifunctional inhibitor, was a potential lead compound for the treatment of AD.


Assuntos
Aminas/química , Desenho de Fármacos , Fármacos Neuroprotetores/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Aminas/metabolismo , Aminas/farmacologia , Aminas/uso terapêutico , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/química , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Chalcona/química , Humanos , Cinética , Metais/química , Metais/metabolismo , Simulação de Acoplamento Molecular , Monoaminoxidase/química , Monoaminoxidase/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Agregados Proteicos/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade
17.
Ecotoxicol Environ Saf ; 215: 112134, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33721662

RESUMO

Rare Earth Elements (REE) increasing demand prompts the research of biotechnological approaches to exploit secondary resources. We made use of the adapted Fluctuation analyses experiment to obtain Chlamydomonas reinhardtii ChlA strains resistant to Samarium (Sm) as the reference REE. The starting hypothesis was that adaptation to metal-containing media leads to an enhanced metal uptake. ChlA was able to adapt to 1.33·10-4 Sm M and pH~3 by pre-existing genetic variability, allowing the evolutionary rescue of 13 of the 99 populations studied. The rescuing resistant genotypes presented a mutation rate of 8.65·10-7 resistant cells per division. The resulting resistant population contradicted the expected fitness cost associated with the adaptation to Sm, selection resulted in larger and faster-growing resistant cells. Among the three isolated strains studied for Sm uptake, only one presented uplifted performance compared to the control population (46.64 µg Sm g-¹ of wet biomass and 3.26·10-7 ng Sm per cell, mainly bioaccumulated within the cells). The selection of microalgae strains with improved tolerance to REEs by this methodology could be a promising solution for REES sequestration. However, increased tolerance can be independent or have negative effects on uptake performance and cellular features studied are not directly correlated with the metal uptake. SUMMARY SENTENCE: Repurposing a classic laboratory evolution experiment to select for microalgae Samarium adapted strains for metals recovery and biotechnology approaches. DATA AVAILABILITY STATEMENT: All data generated or analyzed during this study are included in this published article (and its raw files).


Assuntos
Microalgas/metabolismo , Samário/metabolismo , Poluentes Químicos da Água/metabolismo , Transporte Biológico , Chlamydomonas reinhardtii , Células Clonais/química , Metais/metabolismo , Metais Terras Raras/análise
18.
Ecotoxicol Environ Saf ; 215: 112165, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773149

RESUMO

BACKGROUND: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent. OBJECTIVES: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters. MATERIALS AND METHODS: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman's correlation. RESULTS: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility. CONCLUSIONS: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements.


Assuntos
Exposição Ambiental , Metaloides/toxicidade , Metais/toxicidade , Sêmen/efeitos dos fármacos , Adulto , Arsênio/sangue , Líquidos Corporais , Cádmio/farmacologia , Estudos Transversais , Humanos , Masculino , Mercúrio , Metaloides/metabolismo , Metais/metabolismo , Níquel/farmacologia , Selênio , Análise do Sêmen , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Vanádio
20.
Mol Cell ; 81(7): 1534-1547.e4, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577776

RESUMO

Cancers with hereditary defects in homologous recombination rely on DNA polymerase θ (pol θ) for repair of DNA double-strand breaks. During end joining, pol θ aligns microhomology tracts internal to 5'-resected broken ends. An unidentified nuclease trims the 3' ends before synthesis can occur. Here we report that a nuclease activity, which differs from the proofreading activity often associated with DNA polymerases, is intrinsic to the polymerase domain of pol θ. Like the DNA synthesis activity, the nuclease activity requires conserved metal-binding residues, metal ions, and dNTPs and is inhibited by ddNTPs or chain-terminated DNA. Our data indicate that pol θ repurposes metal ions in the polymerase active site for endonucleolytic cleavage and that the polymerase-active and end-trimming conformations of the enzyme are distinct. We reveal a nimble strategy of substrate processing that allows pol θ to trim or extend DNA depending on the DNA repair context.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA Polimerase Dirigida por DNA/metabolismo , DNA/metabolismo , Endonucleases/metabolismo , Metais/metabolismo , Linhagem Celular , DNA/genética , DNA Polimerase Dirigida por DNA/genética , Endonucleases/genética , Humanos
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