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1.
Int J Nanomedicine ; 15: 5613-5627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884257

RESUMO

Background: Stimuli-responsive gold nano-assemblies have attracted attention as drug delivery systems in the biomedical field. However, there are challenges achieving targeted delivery and controllable drug release for specific diseases. Materials and Methods: In this study, a glutathione (GSH)-modified fluorescent gold nanoparticle termed AuLA-GSH was prepared and a Co2+-induced self-assembly drug delivery platform termed AuLA-GSH-Co was constructed. Both the pH-responsive character and drug loading behavior of AuLA-GSH-Co were studied in vitro. Kidney-targeting capability was investigated in vitro and in vivo. Finally, the anti-fibrosis efficiency of AuLA-GSH-Co in a mouse model of unilateral ureteral obstruction (UUO) was explored. Results: AuLA-GSH-Co was sensitive to pH changes and released Co2+ in acidic conditions, allowing it to have controllable drug release abilities. AuLA-GSH-Co was found to improve cellular uptake of Co2+ ions compared to CoCl2 in vitro. AuLA-GSH exhibited specific renal targeting and prolonged renal retention time with low non-specific accumulation in vivo. Moreover, the anti-fibrosis efficiency of AuLA-GSH-Co was higher compared to CoCl2 in a mouse model of unilateral ureteral obstruction (UUO). Conclusion: AuLA-GSH-Co could greatly enhance drug delivery efficiency with renal targeting capability and obviously relieve renal fibrosis, providing a promising strategy for renal fibrosis therapy.


Assuntos
Cobalto/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nefropatias/tratamento farmacológico , Rim/patologia , Nanopartículas Metálicas/química , Animais , Linhagem Celular , Cobalto/química , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fibrose , Fluorescência , Glutationa/química , Ouro/química , Concentração de Íons de Hidrogênio , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/patologia , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos BALB C , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Sistema Fagocitário Mononuclear/metabolismo , Ratos , Obstrução Ureteral
2.
Chem Res Toxicol ; 33(10): 2668-2674, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32894672

RESUMO

Inflammation is an immune response to protect against various types of infections. When unchecked, acute inflammation can be life-threatening, as seen with the current coronavirus pandemic. Strong oxidants, such as peroxynitrite produced by immune cells, are major mediators of the inflammation-associated pathogenesis. Cellular thiols play important roles in mitigating inflammation-associated macromolecular damage including DNA. Herein, we have demonstrated a role of glutathione (GSH) and other thiols in neutralizing the effect of peroxynitrite-mediated DNA damage through stable GSH-DNA adduct formation. Our observation supports the use of thiol supplements as a potential therapeutic strategy against severe COVID-19 cases and a Phase II (NCT04374461) open-label clinical trial launched in early May 2020 by the Memorial Sloan Kettering Cancer Center.


Assuntos
Adutos de DNA/efeitos dos fármacos , DNA/efeitos dos fármacos , Glutationa/farmacologia , Inflamação/fisiopatologia , Ácido Peroxinitroso/efeitos adversos , Doença Aguda , Animais , Betacoronavirus , Bovinos , Infecções por Coronavirus/tratamento farmacológico , DNA/química , Adutos de DNA/química , Dano ao DNA , Glutationa/química , Células HEK293 , Humanos , Mutagênicos/química , Mutagênicos/farmacologia , Pandemias , Ácido Peroxinitroso/química , Pneumonia Viral/tratamento farmacológico , Salmonella typhimurium/genética
3.
Proc Natl Acad Sci U S A ; 117(32): 19228-19236, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32703810

RESUMO

The ATP-binding cassette (ABC) transporter of mitochondria (Atm1) mediates iron homeostasis in eukaryotes, while the prokaryotic homolog from Novosphingobium aromaticivorans (NaAtm1) can export glutathione derivatives and confer protection against heavy-metal toxicity. To establish the structural framework underlying the NaAtm1 transport mechanism, we determined eight structures by X-ray crystallography and single-particle cryo-electron microscopy in distinct conformational states, stabilized by individual disulfide crosslinks and nucleotides. As NaAtm1 progresses through the transport cycle, conformational changes in transmembrane helix 6 (TM6) alter the glutathione-binding site and the associated substrate-binding cavity. Significantly, kinking of TM6 in the post-ATP hydrolysis state stabilized by MgADPVO4 eliminates this cavity, precluding uptake of glutathione derivatives. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport by NaAtm1. One of the disulfide crosslinked NaAtm1 variants characterized in this work retains significant glutathione transport activity, suggesting that ATP hydrolysis and substrate transport by Atm1 may involve a limited set of conformational states with minimal separation of the nucleotide-binding domains in the inward-facing conformation.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Proteínas de Bactérias/química , Sphingomonadaceae/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Glutationa/química , Glutationa/metabolismo , Ferro/metabolismo , Domínios Proteicos , Sphingomonadaceae/química , Sphingomonadaceae/genética
4.
Food Chem ; 329: 127171, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502745

RESUMO

The inhibition effects of glutathione (GSH) on acrylamide (AA) in the asparagine/glucose model systems and cookies were investigated. The formation of AA was significantly inhibited by GSH addition in the model systems. The decreasing levels of AA were in the range of 38-86%, 57-82%, and 3-41% at 120, 140, and 160 °C, respectively. In addition, the presence of GSH in cookies also inhibited the AA formation, but with no corresponding relationship between the GSH level and the inhibition ratio. The addition of 0.05 g/kg GSH in cookie dough resulted in the decreasing of AA by 48%, some improvement in cookie lightness, but no influence on cookie texture. Kinetic analysis showed that the application of GSH not only inhibited the formation of AA but also improved the elimination of AA. In the summary, GSH could be a potential inhibitor to reduce the AA formation in food during the heating process.


Assuntos
Acrilamida/química , Asparagina/química , Culinária , Glucose/química , Glutationa/química , Acrilamida/metabolismo , Asparagina/metabolismo , Indústria de Processamento de Alimentos , Glucose/metabolismo , Glutationa/metabolismo , Cinética
5.
PLoS One ; 15(5): e0233289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469899

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two aggregates, namely, amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein (tau-p), which are released into the blood in a very small amount and cannot be easily detected. An increasing number of recent studies have suggested that S-glutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is highly correlated with Aß in patients with AD and that S-glutathionylated GAPDH plays a role as a proapoptotic factor in AD. We found that S-glutathionylated GAPDH is abundant in the blood of AD patients, which is unusual because S-glutathionylated GAPDH cannot exist in the blood under normal conditions. The aim of this study was to further explore the correlation between the S-glutathionylated GAPDH levels in blood plasma and AD progression. As controls, we recruited 191 people without AD, which included 111 healthy individuals and 37 patients with depression and insomnia, in the psychosomatic clinic. Moreover, 47 patients with AD (aged 40-89 years) were recruited at the neurology clinic. The blood S-glutathionylated GAPDH levels in the AD patients were significantly (p < 0.001) higher (752.7 ± 301.7 ng/dL) than those in the controls (59.92 ± 122.4 ng/dL), irrespective of gender and age. For AD diagnosis, the criterion blood S-glutathionylated GAPDH level > 251.62 ng/dL exhibited 95.74% sensitivity and 92.67% specificity. In fact, the individuals aged 70-89 years, namely, 37 patients from the psychosomatic clinic and 42 healthy individuals, showed significant blood S-glutathionylated GAPDH levels (230.5 ± 79.3 and 8.05 ± 20.51 ng/dL, respectively). This finding might indicate neurodegenerative AD progression in psychosomatic patients and suggests that the degree of neuronal apoptosis during AD progression might be sensitively evaluated based on the level of S-glutathionylated GAPDH in blood.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Proteínas Sanguíneas/metabolismo , Glutationa/química , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/sangue , Processamento de Proteína Pós-Traducional , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/química , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
J Chromatogr A ; 1622: 461160, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32450990

RESUMO

The glutathione (GSH) trapping assay is commonly utilized for the screening and characterization of reactive metabolites produced by drug metabolism. This study describes a fluorous derivatization method for a more sensitive and selective analysis of reactive metabolites trapped by GSH using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, the GSH-trapped reactive metabolites, which were obtained after incubation of the test compounds with human liver microsome (HLM) in the presence of GSH and NADPH, were derivatized using the perfluoroalkylamine reagent through oxazolone chemistry. Since this reaction enabled the selective modification of the α-carboxyl group in GSH, the structural compositions of the metabolites were not affected by the derivatization. Furthermore, the selective analysis of the resulting derivatives could be performed using perfluoroalkyl-modified stationary phase LC separation via the interaction between the perfluoroalkyl-containing compounds, such as fluorous affinity, followed by detection with the precursor ion and/or enhanced product ion scan modes in MS/MS. Finally, we demonstrated the applicability of this method by analyzing perfluoroalkyl derivatives of some drug metabolites trapped by GSH in HLM incubation.


Assuntos
Cromatografia Líquida/métodos , Flúor/química , Glutationa/análise , Espectrometria de Massas em Tandem/métodos , Glutationa/química , Humanos , Microssomos Hepáticos/metabolismo , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo
7.
Food Chem ; 326: 126982, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32413762

RESUMO

Glutathione (GSH) is a potential inhibitor for acrylamide (AA) in heated food. In the present study, the inhibition pathways of GSH on AA were investigated in the asparagine(Asn)/glucose(Glc)/GSH model system. In comparison to the Asn/Glc model system, three unique molecular ions (m/z 470, 379, and 193) were identified in the Asn/Glc/GSH model system. Those molecular ions were confirmed as the Amadori rearrangement products which formed in the reaction between Glc and GSH, as well as the addition reaction products between AA and the sulfhydryl group (-SH) of GSH and cysteine (Cys). The competition between Asn and GSH for Glc in the competitive reactions was assumed to be the major pathway. Additionally, the elimination reaction between AA and GSH or between AA and Cys also played a minor role in the inhibition of AA. The variances of precursors, intermediates, and final products provided quantitative evidence for the above pathways.


Assuntos
Acrilamida/antagonistas & inibidores , Glutationa/química , Acrilamida/metabolismo , Asparagina/química , Glucose/química , Glutationa/metabolismo , Compostos de Sulfidrila/química , Espectrometria de Massas em Tandem , Temperatura
8.
Nat Commun ; 11(1): 1725, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265442

RESUMO

Class I glutaredoxins are enzymatically active, glutathione-dependent oxidoreductases, whilst class II glutaredoxins are typically enzymatically inactive, Fe-S cluster-binding proteins. Enzymatically active glutaredoxins harbor both a glutathione-scaffold site for reacting with glutathionylated disulfide substrates and a glutathione-activator site for reacting with reduced glutathione. Here, using yeast ScGrx7 as a model protein, we comprehensively identified and characterized key residues from four distinct protein regions, as well as the covalently bound glutathione moiety, and quantified their contribution to both interaction sites. Additionally, we developed a redox-sensitive GFP2-based assay, which allowed the real-time assessment of glutaredoxin structure-function relationships inside living cells. Finally, we employed this assay to rapidly screen multiple glutaredoxin mutants, ultimately enabling us to convert enzymatically active and inactive glutaredoxins into each other. In summary, we have gained a comprehensive understanding of the mechanistic underpinnings of glutaredoxin catalysis and have elucidated the determinant structural differences between the two main classes of glutaredoxins.


Assuntos
Glutarredoxinas/química , Glutationa/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimologia , Sequência de Aminoácidos/genética , Catálise , Domínio Catalítico/genética , Dissulfetos/química , Ativação Enzimática , Ensaios Enzimáticos , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Glutationa/química , Cinética , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Oxirredução , Conformação Proteica em alfa-Hélice , Saccharomyces cerevisiae/citologia , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
9.
Acta Cir Bras ; 35(1): e202000101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159587

RESUMO

Solid organ transplantation is a very complex process, in which the storage of the graft in a preservation solution is mandatory in order to extend ischemic times and contain further damage. The condition in which the organ is transplanted is critical for the outcome of the organ recipient. The recent emergence of generic versions of organ preservation solutions (solutions with the same composition and under the same legislation as the original versions, but with different brands) compelled us to study whether the standards are maintained when comparing the original and its generic counterpart. Along these lines, we discuss and comment on some aspects concerning this issue of general interest in the organ transplantation field.


Assuntos
Glutationa/química , Soluções para Preservação de Órgãos/química , Transplante de Órgãos/métodos , Cálcio/análise , Humanos , Soluções para Preservação de Órgãos/normas , Temperatura , Fatores de Tempo
10.
Food Chem ; 319: 126540, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32151899

RESUMO

SeMet-Pro-Ser (Se-MPS) is an antioxidant selenopeptide derived from selenized brown rice protein hydrolysates. In this study, the stability of glutathione (GSH), Met-Pro-Ser (MPS), and Se-MPS under different processing conditions, namely, temperature, pH, NaCl, citric acid, light, and gastrointestinal proteases, were evaluated by measuring ABTS+ scavenging and Cr(VI) reduction capacities. The ABTS+ scavenging capacity of GSH under thermal treatment, high salt density, and long-term storage was significantly decreased, while its Cr(VI) reduction activity was relatively stable. No significant change of Se-MPS antioxidant activity was observed under different conditions, except under citric acid. Meanwhile, its Cr(VI) reduction activity was partially or mostly retained under different treatment conditions. However, it displayed negligible ABTS+ scavenging capacity. Se-MPS was superior to GSH and MPS in terms of stability and antioxidant activity and could be a candidate for development of nutraceuticals or functional food.


Assuntos
Antioxidantes/química , Dipeptídeos/química , Oryza/enzimologia , Peptídeos/química , Hidrolisados de Proteína/metabolismo , Antioxidantes/metabolismo , Dipeptídeos/metabolismo , Glutationa/química , Oryza/química , Peptídeos/metabolismo
11.
Talanta ; 212: 120583, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113570

RESUMO

Selenocysteine (Sec) is a primary kind of reactive selenium species in cells, and its vital roles in physiological processes have been characterized. Therefore, the highly effective method for sensing Sec in metabolic processes and selenium-rich food must be developed. This study presents a new fluorescent probe, namely, GSH-NB@AuNPs, for highly selective detection of selenol based on the fluorescence quenching quality on the surface of gold nanoparticles (AuNPs). The probe consists of glutathione (GSH) and Nile blue (NB) moieties assembled on AuNPs. The probe exhibits excellent sensitivity and selectivity for Sec and is applied in imaging endogenous and exogenous Sec in living cells through confocal fluorescence microscopy. The proposed probe provides a promising and powerful method for detecting selenol in foodstuff (such as selenium-rich rice and tea) with the detection limit of 9.5 nM.


Assuntos
Corantes Fluorescentes/química , Glutationa/química , Nanopartículas Metálicas/química , Oxazinas/química , Selenocisteína/análise , Ouro/química , Células Hep G2 , Humanos , Limite de Detecção , Microscopia de Fluorescência , Oryza/química , Selenocisteína/química , Espectrometria de Fluorescência , Chá/química
12.
Org Biomol Chem ; 18(13): 2468-2474, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167516

RESUMO

A new N2O-type BODIPY probe (LF-Bop) has been proposed for the selective and sensitive detection of biologically relevant small molecular thiols. This detection is based on the Michael addition reaction between the thiol and nitrostyrene groups in the probe, which decreases the quenching effect from the nitro group, thus resulting in the recovery of the deep-red fluorescence from the BODIPY structure. The results show that LF-Bop is able to detect all tested free thiols through a fluorescence turn-on assay. The lowest limit of detection (LOD) for glutathione was found to be down to nanomolar levels (220 nM). Based on this probe, we have developed a new fluorescence assay for the screening of acetylcholinesterase inhibitors. In total, 11 natural and synthetic alkaloids have been evaluated. Both experimental measurements and theoretical molecular docking results reveal that both natural berberine and its synthetic derivative dihydroberberine are potential inhibitors of acetylcholinesterase.


Assuntos
Compostos de Boro/química , Inibidores da Colinesterase/química , Corantes Fluorescentes/química , Glutationa/análise , Estirenos/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Animais , Berberina/análogos & derivados , Berberina/química , Berberina/metabolismo , Compostos de Boro/síntese química , Inibidores da Colinesterase/metabolismo , Avaliação Pré-Clínica de Medicamentos , Elasmobrânquios , Peixe Elétrico , Corantes Fluorescentes/síntese química , Glutationa/química , Limite de Detecção , Simulação de Acoplamento Molecular , Ligação Proteica , Estirenos/síntese química , Tacrina/química , Tacrina/metabolismo
13.
Inorg Chem ; 59(7): 4186-4190, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212682

RESUMO

Aß4-42 is the major subspecies of Aß peptides characterized by avid Cu(II) binding via the ATCUN/NTS motif. It is thought to be produced in vivo proteolytically by neprilysin, but in vitro experiments in the presence of Cu(II) ions indicated preferable formation of C-terminally truncated ATCUN/NTS species including CuIIAß4-16, CuIIAß4-9, and also CuIIAß12-16, all with nearly femtomolar affinities at neutral pH. Such small complexes may serve as shuttles for copper clearance from extracellular brain spaces, on condition they could survive intracellular conditions upon crossing biological barriers. In order to ascertain such possibility, we studied the reactions of CuIIAß4-16, CuIIAß4-9, CuIIAß12-16, and CuIIAß1-16 with reduced glutathione (GSH) under aerobic and anaerobic conditions using absorption spectroscopy and mass spectrometry. We found CuIIAß4-16 and CuIIAß4-9 to be strongly resistant to reduction and concomitant formation of Cu(I)-GSH complexes, with reaction times ∼10 h, while CuIIAß12-16 was reduced within minutes and CuIIAß1-16 within seconds of incubation. Upon GSH exhaustion by molecular oxygen, the CuIIAß complexes were reformed with no concomitant oxidative damage to peptides. These finding reinforce the concept of Aß4-x peptides as physiological trafficking partners of brain copper.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Proteínas de Transporte/metabolismo , Cobre/metabolismo , Glutationa/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeos beta-Amiloides/química , Proteínas de Transporte/química , Cobre/química , Glutationa/química , Neprilisina/metabolismo , Oxirredução , Fragmentos de Peptídeos/química
14.
Chem Commun (Camb) ; 56(20): 3081-3084, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32051996

RESUMO

Surface CIEE based on Zn-HDS as host material and GSH-CuNCs as guest molecules was developed to produce fluorescence composite GSH-CuNCs/Zn-HDS for the first time. It displays high quantum yield, long fluorescence lifetime and good stability, and was applied to sensitive bioenzyme sensing and fabrication of a high performance light-emitting diode.


Assuntos
Cobre/química , Enzimas/análise , Corantes Fluorescentes/química , Luz , Nanopartículas Metálicas/química , Zinco/química , Enzimas/metabolismo , Glutationa/química , Tamanho da Partícula , Sais/química , Propriedades de Superfície
15.
Adv Mater ; 32(12): e1907210, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048361

RESUMO

Prodrug nanoparticles that codeliver the immune modulators to the tumor site are highly recommendable for cancer immunotherapy yet remain challenging. However, effective stimuli-responsive strategies that exploit the endogenous hallmarks of the tumor have paved the way for cancer immunotherapy. For the first time, the development of the Boolean logic prodrug nanoparticles (BLPNs) for tumor-targeted codelivery of immune modulators (e.g., immune activator and immune inhibitor) and combination immunotherapy is reported herein. A library of stimuli-activatable BLPNs is fabricated yielding YES/AND logic outputs by adjusting the input combinations, including extracellular matrix metalloproteins 2/9 (MMP-2/9), intracellular acidity (pH = 5.0-6.0), and reduction (glutathione) in the tumor microenvironment. Tunable and selective control over BLPNs dissociation and prodrug activation is achieved by specifying the connectivity of orthogonal stimuli-labile spacers while exploiting the endogenous signals at the tumor sites. The tumor-specific distribution of the BLPNs and stimuli-activation of the immune modulators for highly efficient cancer immunotherapy are further demonstrated. The results reported in this study may open a new avenue for tumor-specific delivery of immune therapeutics and precise cancer immunotherapy.


Assuntos
Fatores Imunológicos/química , Nanopartículas/química , Neoplasias/terapia , Pró-Fármacos/química , Animais , Linhagem Celular Tumoral , Glutationa/química , Humanos , Imidazóis/química , Imidazóis/uso terapêutico , Fatores Imunológicos/metabolismo , Fatores Imunológicos/uso terapêutico , Imunoterapia , Isoindóis/química , Isoindóis/uso terapêutico , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Peptídeos/química , Peptídeos/metabolismo , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Transplante Heterólogo
16.
J Biotechnol ; 310: 103-113, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32023480

RESUMO

The inflammation of chronic wounds generally causes delaying their healing process. The present work aims to formulate a wound dressing polyelectrolyte membrane based on chitosan (Ch) and sodium hyaluronate (HA) loaded with glutathione (GSH). The membrane types (Ch/HA and Ch/HA/GSH) were examined by Fourier transform infrared spectroscopy (FT-IR). The material properties were further investigated using thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). Physical characteristics of the prepared membranes, such as wettability, surface roughness, and mechanical properties were determined by standard experimental methods. In vitro assays were used to evaluate the haemocompatibility, thrombogenicity, and cytotoxicity of the membranes. The wound healing examined using a standard rat model exhibited a progress at exploiting the Ch/HA/GSH-type membranes compared to a bicomponent Ch/HA membrane or a "dry" healing wound. Histological examination of the recovered skin confirmed the visual observations. In conclusion, in vivo study results assert that Ch/HA/GSH is a proper wound-dressing for healing the chronic skin wounds.


Assuntos
Quitosana , Glutationa , Ácido Hialurônico , Membranas Artificiais , Polieletrólitos , Cicatrização/efeitos dos fármacos , Animais , Quitosana/química , Quitosana/farmacologia , Feminino , Glutationa/química , Glutationa/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Polieletrólitos/química , Polieletrólitos/farmacologia , Ratos , Ratos Wistar
17.
Biochim Biophys Acta Gen Subj ; 1864(6): 129560, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32061786

RESUMO

BACKGROUND: We previously showed that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is S-glutathionylated in the presence of H2O2 and GSH. S-glutathionylation was shown to result in the formation of a disulfide bridge in the active site of the protein. In the present work, the possible biological significance of the disulfide bridge was investigated. METHODS: Human recombinant GAPDH with the mutation C156S (hGAPDH_C156S) was obtained to prevent the formation of the disulfide bridge. Properties of S-glutathionylated hGAPDH_C156S were studied in comparison with those of the wild-type protein hGAPDH. RESULTS: S-glutathionylation of hGAPDH and hGAPDH_C156S results in the reversible inactivation of the proteins. In both cases, the modification results in corresponding mixed disulfides between the catalytic Cys152 and GSH. In the case of hGAPDH, the mixed disulfide breaks down yielding Cys152-Cys156 disulfide bridge in the active site. In hGAPDH_C156S, the mixed disulfide is stable. Differential scanning calorimetry method showed that S-glutathionylation leads to destabilization of hGAPDH molecule, but does not affect significantly hGAPDH_C156S. Reactivation of S-glutathionylated hGAPDH in the presence of GSH and glutaredoxin 1 is approximately two-fold more efficient compared to that of hGAPDH_C156S. CONCLUSIONS: S-glutathionylation induces the formation of Cys152-Cys156 disulfide bond in the active site of hGAPDH, which results in structural changes of the protein molecule. Cys156 is important for reactivation of S-glutathionylated GAPDH by glutaredoxin 1. GENERAL SIGNIFICANCE: The described mechanism may be important for interaction between GAPDH and other proteins and ligands, involved in cell signaling.


Assuntos
Catálise , Dissulfetos/química , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/química , Estresse Oxidativo/efeitos dos fármacos , Domínio Catalítico/efeitos dos fármacos , Glutationa/química , Dissulfeto de Glutationa/química , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Humanos , Peróxido de Hidrogênio/química , Oxirredução/efeitos dos fármacos
18.
Talanta ; 211: 120699, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32070559

RESUMO

A progressive aggregation-induced emission (AIE) strategy is established based on two diverse stimulus-responsive patterns of copper nanoclusters (CuNCs) for imaging of aluminum ions (Al3+) in cellular microenvironment. The non-emissive CuNCs were facilely synthesized with l-glutathione (GSH) as both stabilizing agent and reducing agent, and demonstrated the excellent AIE characteristics in the ethanol/water mixture. Moreover, the dispersed CuNCs can be aggregated to give the AIE behavior in aqueous solutions by reducing the pH value, and could be further aggregated with 94-fold reinforce by introducing Al3+ ascribe to the strong coordination ability between Al3+ and the functional groups of GSH, demonstrating the progressive AIE process. Under endocytosis, the progressive AIE strategy can be employed to distinguish the Al3+ in the locations of lysosome against other organelles due to the acidic microenvironment of lysosome. The progressive AIE advantages of CuNCs provide a new concept for signal transduction, and have the promising applications in decoding the functions of intracellular biomolecules.


Assuntos
Alumínio/metabolismo , Microambiente Celular , Cobre/química , Glutationa/química , Nanoestruturas/química , Cobre/toxicidade , Glutationa/toxicidade , Células HeLa , Humanos , Lisossomos/metabolismo , Microscopia Confocal , Nanoestruturas/toxicidade
19.
Environ Sci Pollut Res Int ; 27(8): 8091-8102, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31897980

RESUMO

Zinc is one of the important essential trace minerals to human health due to its antioxidant properties. The present study was conducted to elucidate its potential protective role against maneb-induced nephrotoxicity. For this purpose, animals were randomly divided into four groups of six each. Mice of group I (negative controls) have received daily 0.5 ml of distilled water, a solvent of maneb. Mice of group II (MB) have received 30 mg/kg bw of maneb daily by intraperitoneal way. Mice of group III (MB + Zn) have received the same dose of maneb as group II, along with ZnSO4 (30 mg/kg bw) daily. Mice of group IV (Zn), considered as positive controls, have received the same dose of ZnSO4 as group III daily. Our results revealed that ZnSO4 co-administration to maneb-treated mice decreased kidney levels of malondialdehyde, hydrogen peroxide, protein carbonyls, and advanced oxidation protein products; the levels of non-enzymatic antioxidants like vitamin C, glutathione, and metallothionein. It recovered the alteration of antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and attenuated DNA fragmentation. Furthermore, this essential trace element was also able to alleviate kidney biomarkers' alterations by lowering plasma levels of creatinine, urea, uric acid, and lactate dehydrogenase. In addition, the histopathological changes induced by maneb were improved following zinc administration. Our results indicated that zinc might be beneficial against maneb-induced renal oxidative damage in mice.


Assuntos
Glutationa Peroxidase/química , Glutationa/química , Rim/fisiopatologia , Maneb , Superóxido Dismutase/química , Zinco/química , Animais , Antioxidantes , Dano ao DNA , Glutationa Peroxidase/metabolismo , Camundongos , Estresse Oxidativo , Distribuição Aleatória
20.
Chemosphere ; 246: 125718, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918082

RESUMO

The presence and mobilization of toxic metal cations represents under many aspects a current and important problem in the environmental field. In this research, as cation lead (II) ion was studied. The formation of complexes between glutathione and lead (II) was studied at 25 °C and in 1.00 M NaCl as ionic medium by means of measurements of electromotive force (e.m.f.) of cells containing glass and lead amalgam electrodes. In the same experimental conditions, the protonation constants of glutathione were determined potentiometrically, using a cell containing the glass electrode. In the same experimental conditions, by considering glutathione (GSH) completely deprotonated, four protonation constants were determined. Potentiometric data could be explained by assuming the formation of 1:1 complexes between GSH and Pb2+ and with the participation of hydrogen ions. The stability constants of the assumed complexes were determined. The 1:1 ratio between GSH and lead (II) was confirmed by spectrophotometric investigations. Measurements by Infrared Rays (IR) and protonic Nuclear Magnetic Resonance (1H NMR) provide information on the structure of the found complexes.


Assuntos
Glutationa/metabolismo , Chumbo/metabolismo , Ligantes , Cátions , Glutationa/química , Concentração de Íons de Hidrogênio , Chumbo/química , Espectroscopia de Ressonância Magnética , Potenciometria , Prótons , Espectrofotometria
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