Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.033
Filtrar
1.
Molecules ; 26(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673263

RESUMO

The current research is focused on studying the biological efficacy of flexirubin, a pigment extracted from Chryseobacterium artocarpi CECT 8497.Different methods such as DPPH, H2O2, NO•, O2•-, •OH, lipid peroxidation inhibition by FTC and TBA, ferric reducing and ferrous chelating activity were carried out to evaluate the antioxidant activity of flexirubin. Molecular docking was also carried out, seeking the molecular interactions of flexirubin and a standard antioxidant compound with SOD enzyme to figure out the possible flexirubin activity mechanism. The new findings revealed that the highest level of flexirubin exhibited similar antioxidant activity as that of the standard compound according to the H2O2, •OH, O2•-, FTC and TBA methods. On the other hand, flexirubin at the highest level has shown lower antioxidant activity than the positive control according to the DPPH and NO• and even much lower when measured by the FRAP method. Molecular docking showed that the interaction of flexirubin was in the binding cavity of the SOD enzyme and did not affect its metal-binding site. These results revealed that flexirubin has antioxidant properties and can be a useful therapeutic compound in preventing or treating free radical-related diseases.


Assuntos
Antioxidantes/química , Pigmentos Biológicos/química , Polienos/química , Superóxido Dismutase/química , Compostos de Bifenilo/química , Chryseobacterium/química , Peróxido de Hidrogênio/química , Simulação de Acoplamento Molecular , Óxido Nítrico/química , Picratos/química , Pigmentação/efeitos dos fármacos
2.
J Mater Chem B ; 9(4): 1059-1068, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33400757

RESUMO

Nitric oxide (NO) is an essential signaling molecule with a number of biological functions and holds great promise in biomedical applications. However, NO delivery technologies have been complicated due to the inherent properties of NO which include short half-life and limited transport distance in human tissues. In addition, the biofunctionality of NO is strongly dependent on its concentrations and locations where it is delivered. To achieve controlled NO delivery, many studies have focused on encapsulating NO donors into macromolecular scaffolds or using catalysts to realize in situ NO generation from NO prodrugs. Successful applications have been shown, however NO donor-loaded platforms experience the limitation of finite NO storage capacity. The present study reports the synthesis of a catalyst, copper-doped zeolitic imidazolate framework ZIF-8 (Cu2+/ZIF-8), that is designed to generate NO from naturally occurring endogenous NO donors. By tuning the copper doping percentages, we achieved controlled NO generation from S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). Cu2+/ZIF-8 particles retained their catalytic potency after 5 NO generation cycles and we showed that our copper-doped ZIF-8 catalyst produced a 10-fold increased amount of NO compared with previous reports. As a proof-of-concept study, we demonstrated the ability of copper-doped ZIF-8 to disperse bacterial biofilms in the presence of GSNO.


Assuntos
Cobre/química , Estruturas Metalorgânicas/química , Óxido Nítrico/síntese química , S-Nitrosotióis/química , Estrutura Molecular , Óxido Nítrico/química , Tamanho da Partícula , Propriedades de Superfície , Zeolitas/química
3.
Chemosphere ; 262: 128384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182105

RESUMO

Arsenic (As) polluted food chain has become a serious issue for the growth and development of humans, animals and plants. Nitric oxide (NO) or silicon (Si) may mitigate As toxicity. However, the combined application of NO and Si in mitigating As uptake and phytotoxicity in Brassica juncea is unknown. Hence, the collegial effect of sodium nitroprusside (SNP), a NO donor and Si application on B. juncea growth, gas exchange parameters, antioxidant system and As uptake was examined in a greenhouse experiment. Arsenic toxicity injured cell membrane as signposted by the elevated level of malondialdehyde (MDA) and hydrogen peroxide (H2O2), thus decreasing the growth of stressed plants. Moreover, As stress negatively affected gas exchange parameters and antioxidative system of plants. However, NO or/and Si alleviated As induced oxidative stress through increasing the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione S-transferase (GST), glutathione (GSH), along with thiol and proline synthesis. Furthermore, plants treated with co-application of NO and Si showed improved growth, gas attributes and decreased As uptake under As regimes. The current study highlights that NO and Si synergistically interact to mitigate detrimental effects of As stress through reducing As uptake. Our findings recommend combined NO and Si application in As spiked soils for improvement of plant growth and stress alleviation.


Assuntos
Arsênico/metabolismo , Mostardeira/fisiologia , Óxido Nítrico/química , Silício/química , Poluentes do Solo/metabolismo , Antioxidantes/metabolismo , Arsênico/toxicidade , Ascorbato Peroxidases/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Mostardeira/metabolismo , Doadores de Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Plântula/efeitos dos fármacos , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismo
4.
Int J Mol Sci ; 21(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321752

RESUMO

Ferric nitrobindins (Nbs) selectively bind NO and catalyze the conversion of peroxynitrite to nitrate. In this study, we show that NO scavenging occurs through the reductive nitrosylation of ferric Mycobacterium tuberculosis and Homo sapiens nitrobindins (Mt-Nb(III) and Hs-Nb(III), respectively). The conversion of Mt-Nb(III) and Hs-Nb(III) to Mt-Nb(II)-NO and Hs-Nb(II)-NO, respectively, is a monophasic process, suggesting that over the explored NO concentration range (between 2.5 × 10-5 and 1.0 × 10-3 M), NO binding is lost in the mixing time (i.e., NOkon ≥ 1.0 × 106 M-1 s-1). The pseudo-first-order rate constant for the reductive nitrosylation of Mt-Nb(III) and Hs-Nb(III) (i.e., k) is not linearly dependent on the NO concentration but tends to level off, with a rate-limiting step (i.e., klim) whose values increase linearly with [OH-]. This indicates that the conversion of Mt-Nb(III) and Hs-Nb(III) to Mt-Nb(II)-NO and Hs-Nb(II)-NO, respectively, is limited by the OH--based catalysis. From the dependence of klim on [OH-], the values of the second-order rate constant kOH- for the reductive nitrosylation of Mt-Nb(III)-NO and Hs-Nb(III)-NO were obtained (4.9 (±0.5) × 103 M-1 s-1 and 6.9 (±0.8) × 103 M-1 s-1, respectively). This process leads to the inactivation of two NO molecules: one being converted to HNO2 and another being tightly bound to the ferrous heme-Fe(II) atom.


Assuntos
Proteínas de Bactérias/metabolismo , Hemeproteínas/metabolismo , Mycobacterium tuberculosis/enzimologia , Óxido Nítrico/metabolismo , Proteínas de Bactérias/química , Hemeproteínas/química , Humanos , Cinética , Óxido Nítrico/química , Oxirredução , Ácido Peroxinitroso/metabolismo , Ligação Proteica
5.
Proc Natl Acad Sci U S A ; 117(28): 16127-16137, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601214

RESUMO

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.


Assuntos
Adesivos/química , Materiais Revestidos Biocompatíveis/química , Peptídeos/química , Stents , Adesivos/síntese química , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Química Click , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Miócitos de Músculo Liso/citologia , Óxido Nítrico/química , Compostos Organosselênicos/química , Peptídeos/síntese química , Proteínas/química , Coelhos , Stents/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle
6.
Nat Commun ; 11(1): 3535, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669568

RESUMO

Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrict Mtb growth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison of Mtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites in Mtb-infected KCs and that acetylcholine is the top-scoring in Mtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibit Mtb growth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly kills Mtb by reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restricts Mtb growth. Our study demonstrates that the metabolic differences between Mtb-infected AMs and KCs lead to differences in the restriction of Mtb growth.


Assuntos
Autofagia/efeitos dos fármacos , Ornitina/farmacologia , Tuberculose/tratamento farmacológico , Ureia/química , Amônia/química , Animais , Apoptose , Arginase/química , Atropina/farmacologia , Proliferação de Células , Progressão da Doença , Feminino , Imidazóis/farmacologia , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/microbiologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/microbiologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/química , Fosfatidilserinas/química , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/química
7.
Chemistry ; 26(51): 11673-11683, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32433809

RESUMO

Nitric oxide (NO)-derived species play essential roles in regulating cellular responses. Among these species, S-nitrosothiols (including RSNO and HSNO) and nitroxyl (HNO) are especially interesting. Owing to their high reactivity and short survival time, the detection of these molecules in biological settings can be challenging. In this regard, much effort has been invested in exploring novel reactions of RSNO/HSNO/HNO and applying these reactions to develop fluorescence probes. Herein, reported specific reactions of RSNO/HSNO/HNO are summarized and strategies used in the design of fluorescent probes are illustrated. The properties and potential problems of representative probes are also discussed.


Assuntos
Corantes Fluorescentes/química , Óxido Nítrico/química , Óxidos de Nitrogênio/química
8.
Inorg Chem ; 59(12): 8308-8319, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437613

RESUMO

Despite a comprehensive study on the biosynthesis and function of nitric oxide, biological metabolism of nitric oxide, especially when its concentration exceeds the cytotoxic level, remains elusive. Oxidation of nitric oxide by O2 in aqueous solution has been known to yield NO2-. On the other hand, a biomimetic study on the metal-mediated conversion of NO to NO2-/NO3- via O2 reactivity disclosed a conceivable pathway for aerobic metabolism of NO. During the NO-to-NO3- conversion, transient formation of metal-bound peroxynitrite and subsequent release of •NO2 via O-O bond cleavage were evidenced by nitration of tyrosine residue or 2,4-di-tert-butylphenol (DTBP). However, the synthetic/catalytic/enzymatic cycle for conversion of nitric oxide into a nitrite pool is not reported. In this study, sequential reaction of the ferrous complex [(PMDTA)Fe(κ2-O,O'-NO2)(κ1-O-NO2)] (3; PMDTA = pentamethyldiethylenetriamine) with NO(g), KC8, and O2 established a synthetic cycle, complex 3 → {Fe(NO)2}9 DNIC [(PMDTA)Fe(NO)2][NO2] (4) → {Fe(NO)2}10 DNIC [(PMDTA)Fe(NO)2] (1) → [(PMDTA)(NO)Fe(κ2-O,N-ONOO)] (2) → complex 3, for the transformation of nitric oxide into nitrite. In contrast to the reported reactivity of metal-bound peroxynitrite toward nitration of DTBP, peroxynitrite-bound MNIC 2 lacks phenol nitration reactivity toward DTBP. Presumably, the [(PMDTA)Fe] core in {Fe(NO)}8 MNIC 2 provides a mononuclear template for intramolecular interaction between Fe-bound peroxynitrite and Fe-bound NO-, yielding Fe-bound nitrite stabilized in the form of complex 3. This [(PMDTA)Fe]-core-mediated concerted peroxynitrite homolytic O-O bond cleavage and combination of the O atom with Fe-bound NO- reveals a novel and effective pathway for NO-to-NO2- transformation. Regarding the reported assembly of the dinitrosyliron unit (DNIU) [Fe(NO)2] in the biological system, this synthetic cycle highlights DNIU as a potential intermediate for nitric oxide monooxygenation activity in a nonheme iron system.


Assuntos
Complexos de Coordenação/química , Compostos Férricos/química , Compostos Ferrosos/química , Óxido Nítrico/química , Nitritos/química , Poliaminas/química , Complexos de Coordenação/síntese química , Estrutura Molecular , Oxigênio/química
9.
Food Chem ; 322: 126778, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32305007

RESUMO

Zearalenone (ZEN) is highly toxic to humans, and therefore, development of sensitive and effective methods for ZEN quantification in cereal crops is particularly important. Here, an innovative photoelectrochemical (PEC) aptasensor based on simply in-situ conjugated composites of zinc oxide-nitrogen doped graphene quantum dots (ZnO-NGQDs) was constructed. On addition of NGQDs, the composites displayed higher PEC signal with 8.8-fold enhancement than pure ZnO nanoparticles. A sensitive and selective PEC aptasensor was fabricated by combining the composites with ZEN aptamer, which yielded an excellent analytical performance for ZEN detection, with a wide linear range of 1.0 × 10-13-1.0 × 10-7 g mL-1 and a low detection limit of 3.3 × 10-14 g mL-1. Good recoveries were obtained using the PEC aptasensor, which were consistent with those obtained using the national standard method (HPLC-MS). Finally, ZEN in mildewing cereal crops was monitored with the PEC aptasensor, exhibiting good potential for application in cereal crops for early diagnosis.


Assuntos
Aptâmeros de Nucleotídeos/química , Grão Comestível/química , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Fotoquímica/métodos , Zearalenona/análise , Grão Comestível/microbiologia , Farinha/análise , Farinha/microbiologia , Grafite/química , Limite de Detecção , Óxido Nítrico/química , Pontos Quânticos , Óxido de Zinco/química
10.
J Phys Chem Lett ; 11(9): 3198-3202, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32250631

RESUMO

Nitric oxide (NO) can either boost or impede the growth of cancer cells depending on its concentration. Therefore, any anticancer treatment using NO requires precisely controlled NO administration to the target cells in terms of dosage and timing. In this context, photochemically activated NO donors were actively explored, but their detailed NO-releasing dynamics, which is crucial for their use, is not known yet. We determined detailed photoexcitation dynamics of a stable, nontoxic, and water-soluble NO precursor, cysteine-bound Roussin's Red Ester (Cys-RRE), including secondary reactions of the nascent photoproducts. The primary quantum yields of the NO dissociation from the photoexcited Cys-RRE were found to be 24-54% depending on the excitation wavelength; however, the geminate rebinding of NO with the nascent radical reduced the level of biologically available NO to as low as 12%. Such information is useful to achieve efficient NO delivery to practical chemical and biological targets.


Assuntos
Cisteína/efeitos da radiação , Doadores de Óxido Nítrico/efeitos da radiação , Óxido Nítrico/química , Compostos Nitrosos/efeitos da radiação , Cisteína/química , Luz , Doadores de Óxido Nítrico/química , Compostos Nitrosos/química , Espectrofotometria Infravermelho
11.
Inorg Chem ; 59(6): 3631-3641, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32114760

RESUMO

A combination of in silico methods was used to extend the experimental description of the reductive nitrosylation mechanism in ferric hemeproteins with the molecular details of the role of surrounding amino acids. The computational strategy consisted in the estimation of potential energy profiles for the transition process associated with the interactions of the coordinated N(NO) moiety with O(H2O) or O(OH-) as nucleophiles, and with distal amino acids as proton acceptors or affecting the stability of transition states. We inspected the reductive nitrosylation in three representative hemeproteins -sperm whale metmyoglobin, α subunit of human methemoglobin and nitrophorin 4 of Rhodnius prolixus. For each case, classical molecular dynamics simulations were performed in order to obtain relevant reactive conformations, and a potential energy profile for the reactive step was obtained using adiabatic mapping or nudged elastic band approaches at the QM/MM level. Specifically, we report the role of a charged Arg45 of myoglobin in destabilizing the transition state when H2O acts as nucleophile, differently to the neutral Pro43 of the hemoglobin subunit. The case of the nitrophorin is unique in that the access of the required water molecules is scarce, thus, preventing the reaction.


Assuntos
Metemoglobina/química , Metamioglobina/química , Óxido Nítrico/química , Proteínas e Peptídeos Salivares/química , Animais , Teoria da Densidade Funcional , Humanos , Ferro/química , Modelos Químicos , Oxirredução , Rhodnius , Cachalote , Água/química
12.
Biochem J ; 477(6): 1123-1136, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32141496

RESUMO

Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms.


Assuntos
Proteínas de Bactérias/metabolismo , Heme/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/fisiologia , Vibrio cholerae/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação/fisiologia , Biologia Computacional/métodos , Cristalografia por Raios X , Heme/química , Heme/genética , Óxido Nítrico/química , Óxido Nítrico/genética , Estrutura Secundária de Proteína , Vibrio cholerae/química , Vibrio cholerae/genética
13.
Sci Adv ; 6(9): eaay5413, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32133403

RESUMO

Angiogenesis is stimulated by nitric oxide (NO) production in endothelial cells (ECs). Although proangiogenic actions of human mesenchymal stem cells (hMSCs) have been extensively studied, the mechanistic role of NO in this action remains obscure. Here, we used a gelatin hydrogel that releases NO upon crosslinking by a transglutaminase reaction ("NO gel"). Then, the source-specific behaviors of bone marrow versus adipose tissue-derived hMSCs (BMSCs versus ADSCs) were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. The NO gel induced pericyte-like characteristics in BMSCs in contrast to EC differentiation in ADSCs, as evidenced by tube stabilization versus tube formation, 3D colocalization versus 2D coformation with EC tube networks, pericyte-like wound healing versus EC-like vasculogenesis in gel plugs, and pericyte versus EC marker production. These results provide previously unidentified insights into the effects of NO in regulating hMSC source-specific angiogenic mechanisms and their therapeutic applications.


Assuntos
Tecido Adiposo/metabolismo , Células da Medula Óssea/metabolismo , Hidrogéis , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico , Tecido Adiposo/citologia , Antígenos de Diferenciação/metabolismo , Células da Medula Óssea/citologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Gelatina/química , Gelatina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Óxido Nítrico/química , Óxido Nítrico/farmacologia
14.
Nitric Oxide ; 97: 33-47, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32045686

RESUMO

The present study unravels origin of nitric oxide (NO) and the interaction between 24-Epibrassinolide (EBL) and nitrate reductase (NR) for NO production in Indian mustard (Brassica juncea L.) under salinity stress. Two independent experiments were performed to check whether (i) Nitrate reductase or Nitric oxide synthase takes part in the biosynthesis of endogenous NO and (ii) EBL has any regulatory effect on NR-dependent NO biosynthesis in the alleviation of salinity stress. Results revealed that NR-inhibitor tungstate significantly (P ≤ 0.05) decreased the NR activity and endogenous NO content, while NOS inhibitor l-NAME did not influence NO biosynthesis and plant growth. Under salinity stress, inhibition in NR activity decreased the activities of antioxidant enzymes, increased H2O2, MDA, protein carbonyl content and caused DNA damage, implying that antioxidant defense might be related to NO signal. EBL supplementation enhanced the NR activity but did not influence NOS activity, suggesting that NR was involved in endogenous NO production. EBL supplementation alleviated the inhibitory effects of salinity stress and improved the plant growth by enhancing nutrients, photosynthetic pigments, compatible osmolytes, and performance of AsA-GSH cycle. It also decreased the superoxide ion accumulation, leaf epidermal damages, cell death, DNA damage, and ABA content. Comet assay revealed significant (P ≤ 0.05) enhancement in tail length and olive tail moment, while flow cytometry did not showed any significant (P ≤ 0.05) changes in genome size and ploidy level under salinity stress. Moreover, EBL supplementation increased the G6PDH activity and S-nitrosothiol content which further boosted the antioxidant responses under salinity stress. Taken together, these results suggested that NO production in mustard occurred in NR-dependent manner and EBL in association with endogenous NO activates the antioxidant system to counter salinity stress.


Assuntos
Brassinosteroides/metabolismo , Mostardeira/química , Nitrato Redutase/metabolismo , Óxido Nítrico/biossíntese , Estresse Salino , Esteroides Heterocíclicos/metabolismo , Brassinosteroides/química , Inibidores Enzimáticos/farmacologia , Índia , Mostardeira/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Nitrato Redutase/química , Óxido Nítrico/química , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Esteroides Heterocíclicos/química
15.
Anal Chim Acta ; 1104: 38-46, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32106955

RESUMO

Nitric oxide (NO) is an omnipresent signalling molecule in all vertebrates. NO modulates blood flow and neural activity. Nitrite anion is one of the most important sources of NO. Nitrite is reduced to NO by various physiological mechanisms including reduction by hemoglobin in vascular system. In this study, nitrite reductase activity (NRA) of hemoglobin is reported using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in a wide potential window from +0.3 V to -1.3 V (vs. Ag/AgCl). To the best of our knowledge, a detailed look into NRA of hemoglobin is proposed here for the first time. Our results indicated two different regimes for reduction of nitrite by hemoglobin in its Fe(II) and Fe(I) states. Both reactions showed a reversible behaviour in the time scale of the experiments. The first reduction displayed a normal redox behaviour, while the latter one had the characteristics of a catalytic electro-reduction/oxidation. The reduction in Fe(II) state was selected as a tool for comparing the NRA of hemoglobin (Hb) and hemoglobin-S (Hb-S) under native-like conditions in a didodecyldimethyl ammonium bromide (DDAB) liquid crystal film. These investigations lay the prospects and guidelines for understanding the direct electrochemistry of hemoglobin utilizing a simplified mediator-free platform.


Assuntos
Eletroquímica/métodos , Hemoglobinas/química , Óxido Nítrico/química , Nitrito Redutases/análise , Hemoglobina Falciforme/química , Humanos , Cristais Líquidos/química , Oxirredução , Compostos de Amônio Quaternário/química
16.
ACS Appl Mater Interfaces ; 12(8): 9070-9079, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32009376

RESUMO

The development of nonfouling and antimicrobial materials has shown great promise for reducing thrombosis and infection associated with medical devices with aims of improving device safety and decreasing the frequency of antibiotic administration. Here, the design of an antimicrobial, anti-inflammatory, and antithrombotic vascular catheter is assessed in vivo over 7 d in a rabbit model. Antimicrobial and antithrombotic activity is achieved through the integration of a nitric oxide donor, while the nonfouling surface is achieved using a covalently bound phosphorylcholine-based polyzwitterionic copolymer topcoat. The effect of sterilization on the nonfouling nature and nitric oxide release is presented. The catheters reduced viability of Staphylococcus aureus in long-term studies (7 d in a CDC bioreactor) and inflammation in the 7 d rabbit model. Overall, this approach provides a robust method for decreasing thrombosis, inflammation, and infections associated with vascular catheters.


Assuntos
Antibacterianos , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres , Materiais Revestidos Biocompatíveis , Óxido Nítrico , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/crescimento & desenvolvimento , Trombose/prevenção & controle , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Óxido Nítrico/química , Óxido Nítrico/farmacologia , Coelhos
17.
J Recept Signal Transduct Res ; 40(1): 34-41, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31910703

RESUMO

Synthesis of a series of new urea and thiourea compounds have been accomplished by the reaction of 2,3-dihydro-1H-inden-1-amine with various phenyl isocyanates and isothiocyanates. These compounds were evaluated for their antioxidant activity by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and nitric oxide (NO) radical scavenging assay methods including IC50 values. Some of the compounds exhibited potential activity in the two tested methods. Among the series of compounds, urea derivative linked with 4-bromo phenyl ring (4b), and thiourea derivatives bonded with phenyl ring (4e), 4-fluoro phenyl ring (4f) and 4-nitro pheyl ring (4h) were found to exhibit promising anti oxidant activity with low IC50 values. Where four of the title comounds exhibited higher bindig energies than the reference compound (Imatinib) in in silico molecular docking studies with Aromatase. All the synthesized compounds were characterized by IR, 1H, 13C NMR and mass spectral data.


Assuntos
Aminas/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Simulação por Computador , Tioureia/farmacologia , Ureia/farmacologia , Aminas/síntese química , Aminas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/química , Depuradores de Radicais Livres/química , Humanos , Concentração Inibidora 50 , Células MCF-7 , Simulação de Acoplamento Molecular , Óxido Nítrico/química , Picratos/química , Tioureia/síntese química , Tioureia/química , Ureia/síntese química , Ureia/química
18.
Chem Asian J ; 15(3): 327-337, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957936

RESUMO

Microbial secondary metabolites (SMs) have long been viewed as a significant source of novel pharmaceutical and agrochemical molecules. With the increasing availability of genomic data, numerous biosynthetic gene clusters (BGCs) have been discovered. Despite the presence of tens of thousands of BGCs that can theoretically produce extremely diverse SMs, many gene clusters remain in a silent state under axenic culture conditions. Co-culture is a promising research approach as it stimulates the expression of cryptic BGCs to produce novel metabolites and also mimics natural interspecies interactions in a laboratory environment. In recent years, the roles of SMs in microbial communication have caught the attention of researchers and our understanding of microbes and their production of remarkable SMs has improved. SMs may be extensively involved in a variety of communication events among microorganisms. We herein summarize certain representative findings in the field of chemical communication involving SMs in co-culture systems.


Assuntos
Bactérias/química , Metabolismo Secundário , Aspergillus fumigatus/química , Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/virologia , Bactérias/metabolismo , Bactérias/virologia , Montagem e Desmontagem da Cromatina , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Streptomyces/química , Streptomyces/metabolismo , Streptomyces/virologia , Vírus/patogenicidade
19.
Int J Biol Macromol ; 145: 547-557, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31891701

RESUMO

A novel polysaccharide fraction (MSCP2) was extracted and isolated from the roots of Millettia Speciosa Champ. Structural characterization revealed that MSCP2 had an average molecular weight of 2.85 × 104 Da and was composed of fucose, arabinose, galactose, glucose and xylose with a ratio of 2.20: 2.52: 4.04: 87.29: 3.96. Methylation analysis and nuclear magnetic resonance (NMR) analysis showed that the main glycosidic linkage types of MSCP2 were proved to be α-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-Xylp-(1→, →6)-ß-D-Galp-(1→, α-L-Araf-(1→, →3,4)-ß-L-Fucp-(1→ and →4)-α-D-GalpA-(1→. The immunomodulatory assay suggested that MSCP2 could significantly improve the pinocytic capacity and increase the secretion of nitric oxide (NO) and cytokines by regulating the corresponding mRNA expression in RAW 264.7 cells. The data from the membrane receptor assay demonstrated that the potential mechanisms of MSCP2-induced macrophage activation were mainly through toll-like receptor 4 (TLR4), scavenger receptor type A (SRA) and glucan receptor (GR)-mediated signaling pathways. These results suggested that MSCP2 can be developed as a promising immunomodulatory agent in functional foods.


Assuntos
Millettia/química , Polissacarídeos/química , Receptor 4 Toll-Like/genética , Animais , Arabinose/química , Fucose/química , Galactose/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glucanos/genética , Glucose/química , Espectroscopia de Ressonância Magnética , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico/química , Raízes de Plantas/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Células RAW 264.7 , RNA Mensageiro/biossíntese , Receptores Depuradores Classe A/genética , Xilose/química
20.
Biochim Biophys Acta Biomembr ; 1862(5): 183198, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958436

RESUMO

Binding of integrin alphaIIbbeta3 (αiibß3) to its ligands is a highly restricted and regulated mechanism. Any modification of the protein structure yields a dysfunctional role, especially in a redox environment. Here, we examine the effect of nitrosative stress on the αiibß3 reconstituted into nanodiscs. Using single molecule force spectroscopy, we measured the interaction between αiibß3 and its ligand RGD and found that in the presence of exogenous nitric oxide (NO) two force regimes are generated: a low force regime of ~100pN indicating the presence of integrin in a normal status, and a broad spectrum of high force regime (~210-450pN) suggesting the protein modification/aggregation. By high resolution atomic force microscopy imaging, we demonstrate that both NO and nitrite (a stable product formed from NO) are involved in destabilizing the transmembrane protein complex leading to release of αiibß3 from the lipid bilayer and protein aggregation. Our experimental setup opens new ways for testing in a membrane environment the effect of radical species on integrins under clinically relevant conditions.


Assuntos
Estresse Nitrosativo/fisiologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/química , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Integrinas/química , Integrinas/metabolismo , Ligantes , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Microscopia de Força Atômica/métodos , Nitratos/metabolismo , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Oligopeptídeos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/fisiologia , Ligação Proteica , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Nitrogênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...