Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.320
Filtrar
1.
Dokl Biochem Biophys ; 486(1): 197-200, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367820

RESUMO

The oxidative modification of human hemoglobin (Hb) treated with hydrogen peroxide was investigated. Using the mass spectrometry method, the oxidized amino acid residues of the hemoglobin molecule were detected: αTrp14, αTyr24, αArg31, αMet32, αTyr42, αHis45, αHis72, αMet76, αPro77, αLys90, αCys104, αTyr140, ßHis2, ßTrp15, ßTrp37, ßMet55, ßCys93, ßCys112, ßTyr130, ßLys144, and ßHis146. The antioxidant potential of the Hb molecule in the intracellular space and in the blood plasma is discussed.


Assuntos
Hemoglobinas/metabolismo , Peróxido de Hidrogênio/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
2.
Exp Parasitol ; 205: 107748, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442453

RESUMO

Trypanosoma cruzi (the causative agent of Chagas disease) presents a complex life cycle that involves adaptations in vertebrate and invertebrate hosts. As a protozoan parasite of hematophagous insects and mammalian hosts, T. cruzi is exposed to reactive oxygen species (ROS). To investigate the functionality of T. cruzi tartrate-resistant acid phosphatase type 5 (TcACP5), we cloned, superexpressed and purified the enzyme. Purified TcACP5 exhibited a Vmax and apparent Km for pNPP hydrolysis of 7.7 ±â€¯0.2 nmol pNP × µg-1 × h-1 and 169.3 ±â€¯22.6 µM, respectively. The pH dependence was characterized by sharp maximal activity at pH 5.0, and inhibition assays demonstrated its sensitivity to acid phosphatase inhibitors. Similar activities were obtained with saturating concentrations of P-Ser and P-Thr as substrates. The enzyme metabolizes hydrogen peroxide (H2O2) in vitro, and parasites superexpressing this enzyme were more resistant to oxidative stress promoted by H2O2. Taken together, these results suggest that TcACP5 plays a central role in phosphoryl transfer and redox reactions.


Assuntos
Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/fisiologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Trypanosoma cruzi/enzimologia , Sequência de Aminoácidos , Imunofluorescência , Regulação Enzimológica da Expressão Gênica , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Microscopia Confocal , Oxirredução , Especificidade por Substrato , Fosfatase Ácida Resistente a Tartarato/antagonistas & inibidores , Fosfatase Ácida Resistente a Tartarato/química , Transfecção , Trypanosoma cruzi/efeitos dos fármacos
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 762-767, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315738

RESUMO

OBJECTIVE: To explore the protective effect of hydrogen-rich water on the oxidative stress injury of astrocytes in mice and its effect on phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signal pathway. METHODS: In vitro, mice astrocytes were cultured and the logarithmic growth period cells were taken for experiment. (1) Experiment one: some cells were acted by 1.25, 2.50, 5.00, 10.00 µmol/L hydrogen peroxide (H2O2) for 20 minutes to determine the appropriate concentration required for astrocyte damage induced by H2O2; cultivating 3, 6, 9, and 12 hours with hydrogen-rich water of 25, 50, 100, and 200 µmol/L, respectively, to determine the concentration and time of hydrogen-rich water pretreatment; the 50 µmol/L hydrogen-rich water was cultured together with PI3K/Akt signal pathway inhibitors wortmannin (WM) 200 nmol/L or 400 nmol/L to determine the best inhibition concentration of wortmannin. Astrocyte activity was detected by methyl thiazolyl tetrazolium (MTT) colorimetry. (2) Experiment two: some cells were divided into blank control group, H2O2 injury group, hydrogen-rich water pretreatment group (HW+H2O2 group), and co-culture of hydrogen-rich water and wortmannin pretreatment group (HW+WM+H2O2 group). The mRNA expressions of PI3K and Akt were detected by reverse transcription-polymerase chain reaction (RT-PCR); the protein expressions of PI3K, Akt and phosphorylated Akt (p-Akt) were detected by Western Blot. RESULTS: (1) Experiment one: the survival rate of the blank control group was 100%. Cell activity gradually decreased with the increase of H2O2 concentration, and the survival rate of the H2O2 action 20 minutes cells of 2.50 µmol/L was reduced to about 50%, so a cell injury model was established at this concentration. With the increase of hydrogen-rich water pretreatment concentration, and the duration of action, the cell survival rate increased first and then decreased. The cell survival rate was highest when 50 µmol/L hydrogen-rich water was pretreated with 9 hours, so a hydrogen-rich water pre-protection model was established. After 200 nmol/L or 400 nmol/L wortmannin was cultured together with hydrogen-rich water, cell activity was inhibited, and the cell survival rate of 200 nmol/L wortmannin group was no significantly different compared with that of H2O2 injury group, so the astrocyte suppression model was established. (2) Experiment two: compared with the blank control group, the mRNA expressions of PI3K and Akt and the protein expressions of PI3K, Akt and p-Akt were significantly decreased in the H2O2 injury group. Compared with the H2O2 injury group, the PI3K, Akt mRNA expressions and PI3K, Akt, p-Akt protein expressions were significantly increased in the HW+H2O2 group [PI3K mRNA (2-ΔΔCT): 0.843±0.019 vs. 0.631±0.038, Akt mRNA (2-ΔΔCT): 0.591±0.025 vs. 0.558±0.037, PI3K/ß-actin: 1.277±0.008 vs. 0.757±0.004, Akt/ß-actin: 1.308±0.015 vs. 0.682±0.006, p-Akt/ß-actin: 1.210±0.005 vs. 0.614±0.005, all P < 0.05]. The mRNA expressions of PI3K, Akt in the HW+WM+H2O2 group was 0.784±0.159 and 0.556±0.037, respectively, and the protein expressions of PI3K, Akt, p-Akt was 0.715±0.006, 0.686±0.005, and 0.606±0.004, respectively, both were significantly lower than those in HW+H2O2 group (all P < 0.05), and there was no significant difference with H2O2 injury group (all P > 0.05). CONCLUSIONS: Hydrogen-rich water activates the PI3K/Akt pathway, thereby mediates mice astrocytes to exert the biological function of antioxidant.


Assuntos
Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Água/química , Água/farmacologia , Animais , Modelos Animais de Doenças , Peróxido de Hidrogênio/farmacologia , Camundongos
4.
Life Sci ; 232: 116665, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323273

RESUMO

AIMS: Overexpression of the mechanistic target of rapamycin (mTOR), a member of the PIKK (phosphoinositide kinase-related kinase) family, protects cardiomyocytes from cell death induced by pathological stimuli such as ischemia. We previously reported that posttranslational modification of mTOR plays an important role in regulating cardiac mTOR expression. The aim of this study was to see if Tel2 (telomere maintenance 2), a protein that regulates the abundance of PIKKs, confers similar cardioprotective effects as mTOR. Tel2 is not well-characterized in cardiomyocytes, therefore we examined the effects of Tel2 on cardiomyocyte viability under ischemic stress conditions. MATERIALS AND METHODS: We overexpressed Tel2 or silenced Tel2 with siRNA in the HL-1 cardiomyocyte cell line to survey the effects of Tel2 overexpression and downregulation on cell survival during hypoxia. Adult mouse cardiomyocytes transfected with Tel2 adenoviruses were used to test whether Tel2 sufficiently prevented cardiomyocyte cell death against hydrogen peroxide (H2O2). KEY FINDINGS: Overexpressing Tel2 increased mTOR expression with a concomitant increase in mTOR Complex 1 (mTORC1) and mTORC2 activity in HL-1 cells. Tel2 deletion decreased mTOR expression, and mTORC1 and mTORC2 activity accordingly. In both HL-1 cells and adult mouse cardiomyocytes, Tel2 overexpression protected cardiomyocytes under ischemic stress. These effects were mTOR-dependent, as mTOR inhibitors blunted the effects of Tel2. While gene silencing of Tel2 did not affect cell survival under normoxia, Tel2 silencing made cardiomyocytes more vulnerable to cell death under hypoxia. SIGNIFICANCE: Upregulating Tel2 expression increases mTOR-mediated cardiomyocyte survival and targeting Tel2 could be another therapeutic strategy against ischemic heart disease.


Assuntos
Sobrevivência Celular/fisiologia , Miócitos Cardíacos/citologia , Proteínas de Ligação a Telômeros/fisiologia , Adenoviridae/genética , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Inativação Gênica , Peróxido de Hidrogênio/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos , Transdução de Sinais , Proteínas de Ligação a Telômeros/genética , Transfecção
5.
Chemosphere ; 233: 920-935, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340420

RESUMO

The current study aimed to investigate the impacts of different concentrations of GO/PANI nanocomposites (25, 50 and 100 mg L-1), in comparison with GO and PANI, on seed germination behaviors, morpho-physiological and biochemical traits in intact (mucilaginous) and demucilaged seeds, and young seedlings of the medicinal plant Salvia mirzayanii. Upon exposure to GO, seed germination was delayed and reduced, and growth attributes (root and shoot length, shoot fresh weight, and total chlorophyll content) declined, all of which could be attributed to the reductions in water uptake and oxidative stress particularly in demucilaged seeds. A hormetic dose-dependent response was observed for the growth traits in both intact and demucilaged seedlings upon exposure to GO/PANI concentrations, i.e. low-concentration stimulation and high-concentration repression. Elevated levels of H2O2 in shoot tissue of the seedlings exposed to GO and high concentration of GO/PANI, in comparison with those exposed to low levels of GO/PANI and control, were linked with the activities of the antioxidant enzymes SOD, CAT, POD, and total phenolics. Overall, the results showed high toxicity of GO on germination and early growth of S. mirzayani that was more evident in demucilaged seedlings, whereas GO/PANI stimulated germination, and the effects on seedling growth were stimulatory or inhibitory depending on the application dose and presence of mucilage. Furthermore, the capacity of GO/PANI nanocomposites to improve germination and cause a regular porosity pattern in roots accompanied by improved water uptake and early establishment of S. mirzayanii propose potential implications of GO/PANI nanocomposites for seeds/plants in drought-prone ecosystems.


Assuntos
Compostos de Anilina/toxicidade , Antioxidantes/farmacologia , Germinação/efeitos dos fármacos , Grafite/toxicidade , Salvia/metabolismo , Plântula/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Catalase/metabolismo , Clorofila , Peróxido de Hidrogênio/farmacologia , Nanocompostos , Estresse Oxidativo/efeitos dos fármacos , Mucilagem Vegetal/metabolismo , Superóxido Dismutase/metabolismo , Água
6.
Chem Commun (Camb) ; 55(53): 7627-7630, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31194209

RESUMO

We demonstrate for the first time the single-molecule counting of oxidative DNA damage in telomeres from a human cervical carcinoma cell line (HeLa cells). This method exhibits high sensitivity towards oxidative DNA damage with a detection limit as low as 9.3 × 10-17 M and good discrimination capability down to the 0.001% oxidative damage level. Moreover, this method can quantify the number of oxidative damaged bases (34-44) in telomeres in each HeLa cell treated with 1000 µM H2O2.


Assuntos
DNA de Neoplasias/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Telômero/efeitos dos fármacos , Dano ao DNA , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Oxirredução , Relação Estrutura-Atividade
7.
Cell Mol Biol Lett ; 24: 42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236120

RESUMO

Human bronchial epithelium (HBE)-Dp71 anti-sense(AS)cells with stably transfected Dp71 siRNA plasmids were prepared for further exploration of Dp71 biological traits in cells other than PC12. HBE-Dp71AS cells displayed increased DNA damage induced by H2O2. Apoptosis of HBE-Dp71AS cells induced by H2O2 was increased via enhancing caspase 3, caspase 8 and caspase 9. HBE-Dp71AS cells also displayed decreased proliferation and clonogenic formation. RAD51 was proved to be a new binding partner of Dp71 by co-immunoprecipitation (Ip) and immunofluorescence. Reduced RAD51 mRNA and protein levels were observed in HBE-Dp71AS cells. Decreased lamin B1, focal adhesion kinase (FAK), phosphorylated focal adhesion kinase (p-FAK) and phosphorylated protein kinase B (p-AKT) were detected in the HBE-Dp71AS cells, which functioned together with RAD51 as the molecular explanations for the character alterations of HBE-Dp71AS cells.


Assuntos
Apoptose , Dano ao DNA , Distrofina/metabolismo , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Rad51 Recombinase/genética , Linhagem Celular , DNA/efeitos dos fármacos , DNA/metabolismo , Reparo do DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação da Expressão Gênica , Humanos , Peróxido de Hidrogênio/farmacologia , Lamina Tipo B/genética , Fosforilação , Processamento de Proteína Pós-Traducional , Rad51 Recombinase/metabolismo
8.
Chem Biol Interact ; 309: 108706, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31194955

RESUMO

Oxidative-stress-induced osteoblast dysfunction plays an important role in the development and progression of osteoporosis. BTB and CNC homology 1 (Bach1) has been suggested as a critical regulator of oxidative stress; however, whether Bach1 plays a role in regulating oxidative-stress-induced osteoblast dysfunction remains unknown. Thus, we investigated the potential role and mechanism of Bach1 in regulating oxidative-stress-induced osteoblast dysfunction. Osteoblasts were treated with hydrogen peroxide (H2O2) to mimic a pathological environment for osteoporosis in vitro. H2O2 exposure induced Bach1 expression in osteoblasts. Functional experiments demonstrated that Bach1 silencing improved cell viability and reduced cell apoptosis and reactive oxygen species (ROS) production in H2O2-treated cells, while Bach1 overexpression produced the opposite effects. Notably, Bach1 inhibition upregulated alkaline phosphatase activity and osteoblast mineralization. Mechanism research revealed that Bach1 inhibition increased the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling and upregulated heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 mRNA expression. The Bach1 inhibition-mediated protective effect was partially reversed by silencing Nrf2 in H2O2-exposed osteoblasts. Taken together, these results demonstrate that Bach1 inhibition alleviates oxidative-stress-induced osteoblast apoptosis and dysfunction by enhancing Nrf2/ARE signaling activation, findings that suggest a critical role for the Bach1/Nrf2/ARE regulation axis in osteoporosis progression. Our study suggests that Bach1 may serve as a potential therapeutic target for treating osteoporosis.


Assuntos
Elementos de Resposta Antioxidante/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina Básica/antagonistas & inibidores , Fatores de Transcrição de Zíper de Leucina Básica/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Camundongos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
Chem Biol Interact ; 310: 108688, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31173752

RESUMO

Glucagon-like peptide 1 (GLP-1) has neuroprotective properties in Alzheimer's disease (AD). In this study, our aim is to explore the neuroprotective effects of liraglutide, a GLP-1 analogue, on AD-like neurodegeneration induced by H2O2 in human neuroblastoma SH-SY5Y cells. Cytotoxicity was determined by MTT assay and lactate dehydrogenase level was monitored by LDH assay. The level of lipid peroxidation and cell apoptosis rate were measured by malondialdehyde (MDA) assay and Annexin V-FITC/propidium iodide (PI) staining. Western blotting was used to assess the expression of Bcl-2, Bax, caspase-3, tau and the Akt/GSK-3ß. Liraglutide pre-treatment enhanced cell viability with reduced cytotoxicity, lipid peroxidationand and apoptosis. In addition, pre-treatment of liraglutide displayed that increased the expression of the pro-survival Bcl-2 and reduced pro-apoptotic Bax with ameliorated the hyperphosphorylation of tau and Akt/GSK-3ß signaling pathway in H2O2 stressed SH-SY5Y cells. These finding provided evidences that liraglutide protected the H2O2 induced AD-like neurodegeneration through improving Akt/GSK-3ß signaling pathway. These results suggest that liraglutide may have potential values for the treatment for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Liraglutida/uso terapêutico , Neuroblastoma/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Estresse Oxidativo , Linhagem Celular Tumoral , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Neuroblastoma/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/etiologia , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
10.
Gen Physiol Biophys ; 38(4): 281-294, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31219431

RESUMO

In this study, the protective effect of coptisine on the oxidative damage-mediated apoptosis was evaluated in cultured human HaCaT keratinocytes. The results demonstrate that preincubation of cells with coptisine prior to H2O2 stimulation resulted in significant inhibition of cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Coptisine also restored H2O2-induced mitochondrial dysfunction and decrease of ATP production, and prevented apoptosis by inhibiting Bax/Bcl-2 ratio, caspase-3 activity, and poly(ADP-ribose) polymerase degradation. Interestingly, the expressions of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its active form, phosphorylated Nrf2, were strikingly promoted by coptisine in the presence of H2O2, which was associated with a marked increase in the expression of heme oxygenase-1 (HO-1). However, coptisine-induced HO-1 expression was completely abrogated by Nrf2-specific small interfering RNA (Nrf2-siRNA), which suggests that the increased expression of HO-1 by coptisine is Nrf2-dependent. In addition, Nrf2-siRNA transfection significantly eliminated the protective effect of coptisine on H2O2-induced cytotoxicity, and this effect was similar to that by zinc protoporphyrin IX (ZnPP), an HO-1 specific inhibitor. Furthermore, the protective effects of coptisine against H2O2-induced cytotoxicity were abolished by ZnPP, indicating that coptisine protects keratinocytes against oxidative stress-induced injury through activation of the Nrf2/HO-1 signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Berberina/análogos & derivados , Dano ao DNA , Heme Oxigenase-1/metabolismo , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Berberina/farmacologia , Linhagem Celular , Humanos , Peróxido de Hidrogênio/farmacologia , Queratinócitos/enzimologia , Queratinócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
J Agric Food Chem ; 67(25): 6970-6977, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31150237

RESUMO

Huanglongbing (HLB), also known as citrus greening, is a bacterial disease that poses a devastating threat to the citrus industry worldwide. To manage this disease efficiently, we developed and characterized a ternary aqueous solution (TSOL) that contains zinc nitrate, urea, and hydrogen peroxide. We report that TSOL exhibits better antimicrobial activity than commercial bactericides for growers. X-ray fluorescence analysis demonstrates that zinc is delivered to citrus leaves, where the bacteria reside. FTIR and Raman spectroscopy, molecular dynamics simulations, and density functional theory calculations elucidate the solution structure of TSOL and reveal a water-mediated interaction between Zn2+ and H2O2, which may facilitate the generation of highly reactive hydroxyl radicals contributing to superior antimicrobial activity of TSOL. Our results not only suggest TSOL as a potent antimicrobial agent to suppress bacterial growth in HLB-infected trees, but also provide a structure-property relationship that explains the superior performance of TSOL.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Citrus/microbiologia , Nitratos/química , Nitratos/farmacologia , Doenças das Plantas/prevenção & controle , Rhizobiaceae/fisiologia , Compostos de Zinco/química , Compostos de Zinco/farmacologia , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , Rhizobiaceae/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Relação Estrutura-Atividade , Ureia/química , Ureia/farmacologia
12.
Food Chem ; 297: 124955, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253342

RESUMO

This study aimed to investigate the effect of hydrogen peroxide (H2O2) on membrane lipids metabolism and its relation to pulp breakdown development of longan fruit during postharvest storage. Compared to the control longans, H2O2-treated longans showed higher pulp breakdown index, cell membrane permeability, and activities of phospholipase D (PLD), lipase and lipoxygenase (LOX). Moreover, H2O2-treated longans maintained higher levels of pulp phosphatidic acid (PA) and saturated fatty acids (SFA). However, H2O2-treated longans exhibited lower levels of pulp phosphatidylcholine (PC), phosphatidylinositol (PI) and unsaturated fatty acids (USFA), lower index of unsaturated fatty acids (IUFA), and lower ratio of USFA to SFA (U/S). These findings demonstrated that H2O2 caused the increased activities of enzymes involving in membrane lipids degradation and the accelerated decompositions of membrane USFA and phospholipids in longan pulp, which eventually triggered the destruction of the pulp cell membrane structure and the development of pulp breakdown in longans during storage.


Assuntos
Enzimas/metabolismo , Frutas/química , Peróxido de Hidrogênio/farmacologia , Lipídeos de Membrana/metabolismo , Sapindaceae/química , Enzimas/química , Ácidos Graxos/análise , Ácidos Graxos/química , Armazenamento de Alimentos , Frutas/efeitos dos fármacos , Frutas/metabolismo , Peróxido de Hidrogênio/química , Lipase/química , Lipase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoxigenase/química , Lipoxigenase/metabolismo , Lipídeos de Membrana/química , Fosfolipase D/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Sapindaceae/efeitos dos fármacos , Sapindaceae/metabolismo
13.
Life Sci ; 231: 116554, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31194992

RESUMO

AIMS: Several adipokines have been proven to improve the therapeutic efficacy of mesenchymal stromal cells (MSCs) when used to treat ischemic heart disease. Asprosin (ASP) is a newly-discovered adipokine. ASP might also predict the severity of coronary pathology. We investigated the role of ASP on MSCs and the effects of ASP-pretreated MSCs on myocardial infarction (MI). MAIN METHODS: MSCs were labelled with a lentivirus carrying green fluorescent protein (GFP). For in vivo study, after pretreatment with vehicle or ASP, MSCs were injected into infarcted hearts. Cardiac function and fibrosis were then evaluated 4 weeks after the induction of MI and survival of MSCs evaluated after 1 week. MSCs proliferation and migration were investigated after ASP treatment in vitro. MSCs apoptosis induced by hydrogen peroxide (H2O2) was assessed using flow cytometry. KEY FINDINGS: Compared to vehicle-pretreated MSCs, ASP-pretreated MSCs significantly improved the left ventricular ejection fraction (LVEF), and inhibited myocardial fibrosis 4 weeks after MI. ASP pretreatment may have promoted homing of transplanted MSCs. In vitro results showed that ASP had no significant effect on MSC proliferation and migration, but protected these cells from H2O2-induced apoptosis. Among 21 molecules associated with antioxidation and cell death, the antioxidant enzyme SOD2 was significantly upregulated by ASP. Furthermore, ASP treatment inhibited H2O2-induced ROS generation and apoptosis via the activated ERK1/2-SOD2 pathway. SIGNIFICANCE: This is the first evidence that ASP can regulate MSCs function and enhance MSCs therapy for ischemic heart disease. Furthermore, we demonstrate that ASP protects MSCs from oxidative stress-induced apoptosis via the ERK1/2-SOD2 pathway.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Infarto do Miocárdio/terapia , Fragmentos de Peptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Coração/fisiopatologia , Peróxido de Hidrogênio/farmacologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Espécies Reativas de Oxigênio/metabolismo , Função Ventricular Esquerda
14.
Chem Commun (Camb) ; 55(44): 6193-6196, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31070620

RESUMO

Hydrogen sulfide (H2S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2S has been impeded by the lack of appropriate H2S donors that could mimic its slow-releasing process in vivo. Herein, we report the rational design, synthesis, and biological evaluation of a series of thioester-based H2S donors. These cysteine-activated H2S donors release H2S in a slow and controllable manner. Most of the donors comprising an allyl moiety showed significant cytoprotective effects in H9c2 cellular models of oxidative damage. The most potent donor 5e decreased the mitochondrial membrane potential (MMP) loss and lactate dehydrogenase (LDH) release in H2O2-stimulated H9c2 cells. More importantly, donor 5e exhibited a potent cardioprotective effect in an in vivo myocardial infarction (MI) mouse model by reducing myocardial infarct size and cardiomyocyte apoptosis. Taken together, our studies demonstrated that these new allyl thioesters are potential cardioprotective agents by releasing H2S.


Assuntos
Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Ésteres/química , Sulfeto de Hidrogênio/química , Compostos de Sulfidrila/química , Animais , Linhagem Celular , Modelos Animais de Doenças , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/metabolismo , Estresse Oxidativo
15.
Environ Pollut ; 251: 502-509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103010

RESUMO

Benzo[a]pyrene (BaP), a common environmental pollutant, can modulate the immune-associated signal pathway NF-κB, which is one of the critical signal pathways involved in various immune responses. BaP exposure usually generates reactive oxygen species (ROS), but whether ROS are predominantly involved in the modulation mechanism of the NF-κB pathway has not been clearly understood. In this study, an in vivo examination of Oryzias melastigma demonstrated that BaP exposure led to a down-regulation of the NF-κB pathway and increased levels of ROS. Conversely, in vitro results using the medaka liver cell line DIT-29 and a widely applied H2O2 method showed the opposite: up-regulation of the NF-κB pathway. However, the down-regulation of NF-κB upon BaP exposure in vitro was inhibited by the addition of a ROS inhibitor, indicating ROS are involved in the modulation of NF-κB. The discrepancy between in vivo and in vitro results of ROS impacts on NF-κB activation might be related to the concentration and persistence of ROS. Using a modified luminol detection system, BaP was found to generate sustained physiological concentrations of ROS for 24 h, while an H2O2 bolus generated ROS for less than 30 min. Furthermore, a steady-state sub-micromolar H2O2 system (H2O2ss) was developed in parallel as a positive control of ROS, by which H2O2 could be maintained for 24 h. Comparative evaluation using H2O2, H2O2ss and BaP exposures on the medaka cell line with pGL4.32 demonstrated that the persistent physiological concentrations of ROS generated upon BaP exposure or treatment with H2O2ss inhibited the NF-κB pathway, but direct H2O2 exposure had the opposite effect. Moreover, a western-blot assay and EMSA detection further confirmed the modulation of the NF-κB pathway in DIT-29. Taken together, this study shows that BaP exposure inhibits the NF-κB pathway by generating sustained physiological concentrations of ROS.


Assuntos
Benzo(a)pireno/toxicidade , Poluentes Ambientais/toxicidade , NF-kappa B/metabolismo , Oryzias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Linhagem Celular , Regulação para Baixo , Peróxido de Hidrogênio/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Oryzias/imunologia
16.
Chemosphere ; 230: 544-558, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31125883

RESUMO

Plant growth and development could be modulated by minute concentrations of hydrogen peroxide (H2O2) which serves as a signaling molecule for various processes. The present work was conducted with an aim that H2O2 could also modify root morphology, morphology and movement of stomata, photosynthetic responses, activity of carbonic anhydrase, and antioxidant systems in tomato (Solanum lycopersicum L.) plants under copper stress (Cu; 10 or 100 mg kg-1 soil). Roots of 20 d old plants were dipped in 0.1 or 0.5 mM of H2O2 solution for 4 h and then transplanted to the soil filled in earthen pots. High Cu stress (100 mg kg-1 soil) altered root morphology, reduced chlorophyll content and photosynthetic capacity and also affected movement of stomata and generation of antioxidant species at 40 d after transplantation. Further, root dipping treatment of H2O2 to plants under stress and stress-free conditions enhanced accumulation of proline and activity of catalase, peroxidase, and superoxide dismutase, whereas production of superoxide radical (O2•¯) and H2O2 were decreased. Overall, H2O2 treatment improved growth, photosynthesis, metabolic state of the plants which provided tolerance and helped the plants to cope well under Cu stress.


Assuntos
Antioxidantes/metabolismo , Cobre/toxicidade , Peróxido de Hidrogênio/farmacologia , Lycopersicon esculentum/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/toxicidade , Lycopersicon esculentum/enzimologia , Lycopersicon esculentum/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
17.
Cell Prolif ; 52(4): e12624, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31038249

RESUMO

OBJECTIVES: Excessive oxidative stress and diminished antioxidant defences could contribute to age-related tissue damage and various diseases including age-related osteoporosis. Dendrobium officinale polysaccharides (DOPs), a major ingredient from a traditional Chinese medicine, have a great potential of antioxidative activity. In this study, we explore the role of DOP in age-related osteoporosis that remains elusive. MATERIALS AND METHODS: Oxidative stimulation and DOP were used to treat bone marrow mesenchymal stem cells (BMSCs), whose lineage commitment was measured by adipogenic- and osteoblastic-induced differentiation analysis. The oxidative stress and antioxidant capacity of BMSCs under the treatment of DOP were analysed by the level of MDA, SOD. Related mechanism studies were confirmed by qRT-PCR, Western blotting and siRNA transfection. DOP was orally administrated in aged mice whose phenotype was confirmed by micro-CT, immunofluorescence, immunochemistry and calcein double-labelling analysis. RESULTS: Dendrobium officinale polysaccharide treatment markedly increased osteogenic differentiation of BMSCs, while inhibiting adipogenic differentiation. In vitro, DOP could rescue H2O2-induced switch of BMSCs differentiation fate. However, this effect was abolished in BMSCs when interfered with Nrf2 siRNA. Furthermore, administration of DOP to aged mice significantly increased the bone mass and reduced the marrow adipose tissue (MAT) accompanied with decreased oxidative stress of BMSCs. CONCLUSIONS: Our study reveals that DOP can attenuate bone loss and MAT accumulation through NRF2 antioxidant signalling, which may represent as potential therapeutic agent for age-related osteoporosis.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Dendrobium/química , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Adulto , Idoso , Animais , Antioxidantes/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
18.
Phytochemistry ; 164: 122-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125862

RESUMO

A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (-)-idaeusinol A and six undescribed furofuran derivatives named (+/-)-idaeusinol B-D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H2O2-induced neurotoxicity at the concentration of 25 µM. In contrast, (-)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H2O2-induced neurotoxicity at both 25 and 50 µM concentration.


Assuntos
Furanos/farmacologia , Lactonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Rubus/química , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Furanos/química , Furanos/isolamento & purificação , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Lactonas/química , Lactonas/isolamento & purificação , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
19.
J Appl Microbiol ; 127(2): 586-597, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077510

RESUMO

AIMS: The current study aimed to assess the potential of a new high dose ultraviolet (UV) disinfection device to inactivate methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile and a norovirus surrogate on handheld mobile devices, and to compare the efficacy of the UV-C device to hydrogen peroxide disinfection wipes. METHODS AND RESULTS: Suspensions of MRSA, C. difficile spores and a surrogate for norovirus (MS2) were inoculated onto glass or plastic coupons, with or without organic contamination and were exposed to continuous UV-C light for 15-60 s (165-646 mJ cm-2 ) in a self-contained UV-C chamber or treated with hydrogen peroxide wipes. Increasing the UV-C dose from 310 to 650 mJ cm-2 did not result in greater levels of inactivation. UV-C light inactivated all three micro-organisms, in the absence of organic contamination, by >2·9 log. Treatment of MRSA, C. difficile spores or MS2, in the presence of organic contamination, with UV-C light (310-646 mJ cm-2 ) resulted in 2·3-3·7 log reductions. Treatment of MRSA with UV-C light provided levels of inactivation comparable to treatment with hydrogen peroxide wipes used following the manufacturer's instructions. CONCLUSIONS: UV-C light and hydrogen peroxide wipes had strong antimicrobial activity against MRSA, C. difficile spores and a norovirus surrogate, in the presence or absence of organic contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Chemical disinfection wipes are widely used in healthcare facilities, but they are not recommended for use on handheld mobile devices which may harbour pathogenic micro-organisms. The powerful bactericidal, sporicidal and virucidal activity of this high dose UV-C light device, shows that this technology is a promising alternative to chemical disinfectants, particularly for control of MRSA.


Assuntos
Clostridium difficile/efeitos da radiação , Desinfecção , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Norovirus/efeitos da radiação , Raios Ultravioleta , Clostridium difficile/efeitos dos fármacos , Desinfetantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/efeitos da radiação
20.
Artif Cells Nanomed Biotechnol ; 47(1): 1758-1765, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062616

RESUMO

Salidroside (Sal) exerted widely pharmacological effects in multitudinous diseases had been certified. The actual study clarified the protective activity of Sal in H2O2-injured human trabecular meshwork (HTM) cells. HTM cells were disposed with H2O2 to construct an oxidative damage model in vitro. Then, Sal was utilized to administrate HTM cells, and cell viability, apoptosis, apoptosis-interrelated proteins and ROS production were appraised using CCK-8, flow cytometry, western blot and DCFH-DA staining. MiR-27a inhibitor and its control were transfected into HTM cells, and the influences of miR-27a inhibition in HTM cells stimulated with H2O2 and Sal were detected. PI3K/AKT and Wnt/ß-catenin pathways were ultimately investigated to uncover the underlying mechanism. We found that H2O2 evoked HTM cells oxidative damage, as evidenced by repressing cell viability, inducing apoptosis, activating cleaved-caspase-3/-9 expression and increasing ROS production. Sal significantly lightened H2O2-evoked oxidative damage in HTM cells. Additionally, miR-27a was up-regulated by Sal, and miR-27a suppression significantly reversed the protective effect of Sal on H2O2-injured HTM cells. Finally, Sal activated PI3K/AKT and Wnt/ß-catenin pathways through enhancement of miR-27a in H2O2-injured HTM cells. In conclusion, these discoveries suggested that Sal could protect HTM cells against H2O2-evoked oxidative damage by activating PI3K/AKT and Wnt/ß-catenin pathways through enhancement of miR-27a. Highlights H2O2 evokes HTM cells oxidative damage; Sal relieves H2O2-induced oxidative damage in HTM cells; Sal enhances miR-27a expression in H2O2-injured HTM cells; Repressed miR-27a reverses the protective impacts of Sal on H2O2-injured HTM cells; Sal activates PI3K/AKT and Wnt/ß-catenin pathways by increasing miR-27a.


Assuntos
Glucosídeos/farmacologia , Peróxido de Hidrogênio/farmacologia , MicroRNAs/genética , Fenóis/farmacologia , Malha Trabecular/citologia , Malha Trabecular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Malha Trabecular/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA