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1.
J Agric Food Chem ; 68(6): 1609-1620, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31957426

RESUMO

Oxidative stress is known to be a key factor in many neurodegenerative diseases. Inflammation also plays a relevant role in a myriad of pathologies such as diabetes and atherosclerosis. Polyphenols coming from dietary sources, such as pterostilbene, may be beneficial in this type of diseases. However, most of them are rapidly metabolized and excreted, yielding very low phenolic bioavailability what makes it difficult to find out which are the mechanisms responsible for the observed bioactivity. Herein, we evaluate the effects of pterostilbene and its metabolites against H2O2-induced cell damage in human neuroblastoma SH-SY5Y cells and against lipopolysaccharide (LPS)-challenged RAW 264.7 macrophages. Among the metabolites tested, 3-methyl-4'-glucuronate-resveratrol (also called 4'-glucuronate pinostilbene, PIN-GlcAc, 11) prevented neuronal death via attenuation of reactive oxygen species (ROS) levels and increased REDOX activity in neurons. This compound is also able to ameliorate LPS-mediated inflammation on macrophages via inhibition of IL-6 and NO production. Thus, polyphenol from dietary sources could be part of potential functional foods designed to ameliorate the onset and progression of certain neurodegenerative diseases via oxidative stress reduction.


Assuntos
Anti-Inflamatórios/farmacologia , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio/toxicidade , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Neuroblastoma/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/metabolismo
2.
J Agric Food Chem ; 68(1): 117-127, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31820963

RESUMO

Six new quassinoids, named kumulactone F (1), kumulactone G (2), kumulactone H (4), kumulactone I (5), kumulactone J (6), and kumulactone K (7), a pair of undescribed epimers α- and ß-nigakihemiacetal G (3), 15 known quassinoids (8-22), and a mixture of the known compounds α- and ß-neoquassin (23) were separated from the dried stems of the medical plants Picrasma quassioides. The chemical structures of all of the new compounds were established by spectroscopic data analyses (HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD)). Biologically, compounds 9 and 21 showed toxicity toward the Asian citrus psyllid Diaphorina citri Kuwayama with potent activity even equal to that of the positive control (Abamectin), compound 11 exhibited an excellent neuroprotective effect against SH-SY5Y cells which were pretreated by H2O2 with potent activity equal to that of the positive control (Trolox), and none of them showed cytotoxic activity toward the HeLa or A549 cell lines (IC50 > 100 µM).


Assuntos
Hemípteros/efeitos dos fármacos , Inseticidas/farmacologia , Fármacos Neuroprotetores/farmacologia , Picrasma/química , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hemípteros/crescimento & desenvolvimento , Humanos , Peróxido de Hidrogênio/toxicidade , Inseticidas/química , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Quassinas/química
3.
Arch Insect Biochem Physiol ; 103(1): e21639, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31647582

RESUMO

Carbon dioxide (CO2 ) exposure is a common method of anesthesia in studies of Drosophila melanogaster. A number of negative side effects of CO2 anesthesia have been reported. It is not clear whether the length of CO2 anesthesia time affects Drosophila survival in aging research. Here, we examined the potential effect of the CO2 anesthesia time length of 10-150 min. We found that long CO2 exposure could lead to Drosophila death, more significant in males. The longer the anesthesia time is, the longer it takes for flies to wake up. Long-time CO2 anesthesia can reduce the lifespan. Our stress tests showed that long-time CO2 anesthesia can increase the average survival time in both males and females under starvation conditions, but can only increase female lifespan under H2 O2 oxidative stress. Long-time CO2 anesthesia also significantly affects physiological traits, with spontaneous activity increased in females but decreased in males, and reduced female fecundity. Our study suggests that limiting the CO2 anesthesia time and giving enough recovery time before performing physiological tests are important in Drosophila aging research.


Assuntos
Dióxido de Carbono/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Envelhecimento , Anestesia , Animais , Dióxido de Carbono/toxicidade , Drosophila melanogaster/fisiologia , Feminino , Fertilidade/efeitos dos fármacos , Privação de Alimentos , Peróxido de Hidrogênio/toxicidade , Longevidade/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fatores Sexuais , Fatores de Tempo
4.
J Agric Food Chem ; 67(49): 13568-13576, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709793

RESUMO

Astaxanthin (AST) is a fat-soluble and non-vitamin A source of carotenoid that can quench reactive oxygen species and it has strong antioxidant and anti-inflammatory abilities. Herein, we have used H2O2 to establish a model of oxidative damage to RAW 264.7 cells and cells treated with vitamin C as the positive control group. The changes in metabolome were examined using 1H NMR and the results demonstrated that H2O2 treatment and various metabolic pathways such as amino acid, glucose, and glycerolipid metabolism were downregulated, which in turn affected citric acid cycle and energy status. AST could reverse downregulation of some of these metabolic pathways to a certain extent, and reduce cellular oxidative stress and death. The AST group differed from the vitamin C group in regulating d-glutamine, d-glutamic acid, pyruvate, and glycerolipid metabolism. The experimental results help to further understand the antioxidant effects of AST.


Assuntos
Antioxidantes/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Peróxido de Hidrogênio/toxicidade , Macrófagos/química , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Células RAW 264.7 , Xantofilas/farmacologia
5.
Gen Physiol Biophys ; 38(5): 455-460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31595883

RESUMO

Lactic acid bacteria (LAB) are exceptionally important strains in food industry. It is a heterogeneous group sharing same metabolic and physiological properties. They are usually catalase-negative strains, which represents a big disadvantage in food production in comparison with pathogenic bacteria as staphylococci and listeria existing in the same environment, because of the use of hydrogen peroxide as a disinfection agent which is utilized by catalases. We focused on increase in LAB surviving through the disinfection without any positive effect on growth of pathogenic bacteria. In our functional test hydrogen peroxide was used for disinfection. Ten mM thermostable catalase-peroxidase AfKatG was added to solid media to cultivate bacteria afterwards. As predicted there was no difference in the growth of pathogenic bacteria with or without catalase-peroxidase addition to media. However, we showed a huge positive effect on surviving LAB. With addition of AfKatG to solid media we gained 2-38 times higher CFU/ml than in control samples without it. We can assume AfKatG as an excellent supplement for growth media of food strains.


Assuntos
Catalase/metabolismo , Meios de Cultura/farmacologia , Meios de Cultura/toxicidade , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Lactobacillales/efeitos dos fármacos , Lactobacillales/crescimento & desenvolvimento , Peroxidase/metabolismo , Meios de Cultura/química , Estabilidade Enzimática , Lactobacillales/metabolismo
6.
J Agric Food Chem ; 67(44): 12191-12198, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588747

RESUMO

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Alho/química , Extratos Vegetais/administração & dosagem , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Espectrometria de Massas , Metabolômica , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
7.
Pain Res Manag ; 2019: 3173149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565108

RESUMO

Migraine is a prevalent neurological disorder which causes a huge economic burden on society. It is thought to be a neurovascular disease with oxidative stress might be involved. Curcumin, one of the major ingredients of turmeric, has potent antioxidative and anti-inflammatory properties, but whether it could be used as a potential treatment for migraine remains to be explored. In the present study, human umbilical vein endothelial cells (HUVECs) were pretreated with various concentrations of curcumin (0 µM, 10 µM, 20 µM, 30 µM, 40 µM, and 50 µM) for 12 h, thereby exposed to H2O2 (100 µM) for another 12 h. The viability of HUVECs was tested by the CCK-8 assay, and the activities of antioxidant enzymes including superoxide dismutase (SOD) and glutathione (GSH) were also examined. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) were assayed to determine H2O2-induced oxidative stress. In addition, several cell death-related genes (p53, p21, Bax, and Bcl-2) were detected by PCR, and an apoptosis-related protein (caspase3) was evaluated by western blotting. Our results showed that curcumin improved the H2O2-induced decrease of cell viability and antioxidative enzyme activities and decreased the level of oxidative stress. As a conclusion, curcumin could mitigate H2O2-induced oxidative stress and cell death in HUVECs and may be a potential therapeutic drug for migraine.


Assuntos
Antioxidantes/farmacologia , Curcumina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Espécies Reativas de Oxigênio
8.
Life Sci ; 236: 116948, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605711

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a destructive trauma accompanied with local injury. Ginsenoside Rg1 exerts anti-apoptosis and anti-autophagy properties. Our goal was to study the protective mechanism of Rg1 in attenuating cell injury. METHODS: MiR-216a-5p inhibitor was transfected into PC-12 cells to verify the growth promoting roles of miR-216a-5p, then cells were pre-treated by Rg1 for 24 h and treated by 300 µM hydrogen peroxide (H2O2) for 1 h. Cell viability and apoptosis were tested through Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Expression of miR-216a-5p and cell damage relative factors was tested via qRT-PCR and Western blot experiments. RESULTS: H2O2 induced cell activity suppression, apoptosis and clear autophagy well at the concentration of 300 µM Rg1 attenuated H2O2-induced cell injury at the concentration of 200 µM that it elevated cell activity, attenuated apoptosis and autophagy and activated phosphatidylinositol 3 kinase (PI3K)/AMP-activated protein kinase (AKT) and AMP-activated protein kinase (AMPK) signal pathways. Further, miR-216a-5p was up-regulated by Rg1. CONCLUSION: Our study demonstrated that Rg1 attenuated H2O2-caused cell injury through positively regulated miR-216a-5p.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia , Fármacos do Sistema Nervoso Central/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Peróxido de Hidrogênio/toxicidade , MicroRNAs/genética , Animais , Oxidantes/toxicidade , Células PC12 , Ratos , Transdução de Sinais
9.
Nat Commun ; 10(1): 4073, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501427

RESUMO

Several antitumor therapies work by increasing reactive oxygen species (ROS) within the tumor micromilieu. Here, we reveal that L-plastin (LPL), an established tumor marker, is reversibly regulated by ROS-induced thiol oxidation on Cys101, which forms a disulfide bridge with Cys42. LPL reduction is mediated by the Thioredoxin1 (TRX1) system, as shown by TRX1 trapping, TRX1 knockdown and blockade of Thioredoxin1 reductase (TRXR1) with auranofin. LPL oxidation diminishes its actin-bundling capacity. Ratiometric imaging using an LPL-roGFP-Orp1 fusion protein and a dimedone-based proximity ligation assay (PLA) reveal that LPL oxidation occurs primarily in actin-based cellular extrusions and strongly inhibits cell spreading and filopodial extension formation in tumor cells. This effect is accompanied by decreased tumor cell migration, invasion and extracellular matrix (ECM) degradation. Since LPL oxidation occurs following treatment of tumors with auranofin or γ-irradiation, it may be a molecular mechanism contributing to the effectiveness of tumor treatment with redox-altering therapies.


Assuntos
Actinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neoplasias/metabolismo , Alquilação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Extensões da Superfície Celular/metabolismo , Cisteína/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Modelos Biológicos , Mutação/genética , Oxirredução , Compostos de Sulfidrila/metabolismo , Tiorredoxina Redutase 1/metabolismo
10.
Mol Cells ; 42(9): 672-685, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31486328

RESUMO

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygenglucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.


Assuntos
Carbonil Redutase (NADPH)/metabolismo , Transplante de Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/terapia , Regulação para Cima , Adulto , Oxirredutases do Álcool/genética , Animais , Biópsia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Glucose/deficiência , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Doadores Vivos , Luteolina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Oxigênio , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
11.
J Appl Oral Sci ; 27: e20180453, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411261

RESUMO

OBJECTIVE: This study was designed for the chemical activation of a 35% hydrogen peroxide (H2O2) bleaching gel to increase its whitening effectiveness and reduce its toxicity. METHODOLOGY: First, the bleaching gel - associated or not with ferrous sulfate (FS), manganese chloride (MC), peroxidase (PR), or catalase (CT) - was applied (3x 15 min) to enamel/dentin discs adapted to artificial pulp chambers. Then, odontoblast-like MDPC-23 cells were exposed for 1 h to the extracts (culture medium + components released from the product), for the assessment of viability (MTT assay) and oxidative stress (H2DCFDA). Residual H2O2 and bleaching effectiveness (DE) were also evaluated. Data were analyzed with one-way ANOVA complemented with Tukey's test (n=8. p<0.05). RESULTS: All chemically activated groups minimized MDPC-23 oxidative stress generation; however, significantly higher cell viability was detected for MC, PR, and CT than for plain 35% H2O2 gel. Nevertheless, FS, MC, PR, and CT reduced the amount of residual H2O2 and increased bleaching effectiveness. CONCLUSION: Chemical activation of 35% H2O2 gel with MC, PR, and CT minimized residual H2O2 and pulp cell toxicity; but PR duplicated the whitening potential of the bleaching gel after a single 45-minute session.


Assuntos
Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/toxicidade , Clareadores Dentários/química , Clareadores Dentários/toxicidade , Clareamento Dental/métodos , Análise de Variância , Catalase/química , Sobrevivência Celular , Células Cultivadas , Cloretos/química , Cor , Polpa Dentária/química , Polpa Dentária/diagnóstico por imagem , Dentina/química , Dentina/efeitos dos fármacos , Compostos Ferrosos/química , Compostos de Manganês/química , Odontoblastos/efeitos dos fármacos , Peroxidase/química , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo
12.
Int J Nanomedicine ; 14: 4491-4502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417254

RESUMO

Background: Selenium (Se) can exert antioxidative activity and prevent the body from experiencing oxidative injury. Biogenic Se nanoparticles (SeNPs) synthesized by probiotics possess relatively strong chemical stability, high bioavailability, and low toxicity, this makes them potential Se supplements. Previously, we demonstrated that SeNPs synthesized by Lactobacillus casei ATCC 393 can alleviate hydrogen peroxide (H2O2)-induced human and porcine intestinal epithelial cells' oxidative damage. However, the antioxidant mechanism remains unclear. Methods: The possible antioxidant mechanism and protective effect of SeNPs on intestinal epithelial permeability and mitochondrial function were evaluated by establishing an H2O2-induced oxidative damage model of human colon mucosal epithelial cells (NCM460) and conducting Nrf2 inhibitor interference experiments. Mitochondrial membrane potential (MMP), mitochondrial DNA content, adenosine triphosphate (ATP), ROS, and protein expression levels of Nrf2-related genes were determined. Mitochondrial ultrastructure was visualized by transmission electron microscopy. Results: An amount of 4 µg Se/mL of SeNPs synthesized by L. casei ATCC 393 alleviated increase of ROS, reduced ATP and MMP, and maintained intestinal epithelial permeability in NCM460 cells challenged by H2O2. In addition, SeNPs improved the protein levels of Nrf2, HO-1, and NQO-1. Moreover, SeNPs attenuated the damage of mitochondrial ultrastructure caused by oxidative stress. Nrf2 inhibitor (ML385) abolished the regulatory effect of SeNPs on intracellular ROS production. Conclusion: Data suggest that biogenic SeNPs synthesized by L. casei ATCC 393 can protect the intestinal epithelial barrier function against oxidative damage by alleviating ROS-mediated mitochondrial dysfunction via Nrf2 signaling pathway. Biogenic SeNPs are an attractive candidate for potential Se supplement agent in preventing oxidative stress-related intestinal disease by targeting mitochondria.


Assuntos
Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Lactobacillus casei/metabolismo , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Selênio/farmacologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Modelos Biológicos , Nanopartículas/ultraestrutura , Oxirredução , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Suínos
13.
Int J Immunopathol Pharmacol ; 33: 2058738419872624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456460

RESUMO

It is of significance to alleviate oxidative damages for the treatment of spinal cord injury (SCI). Studies have ascertained that green tea polyphenols (GTPs) exert protective activities against oxidative damages. In this study, we aimed to investigate the protective effects of GTP against H2O2-caused injuries in PC12 cells as well as the molecular underpinnings associated with long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). PC12 cells were preincubated with GTP prior to H2O2 stimulation. Furthermore, MALAT1-deficient PC12 cells were constructed by transfection and identified by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Next, viability and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. Meanwhile, Western blot assay was carried out to monitor the expression alteration of proteins associated with apoptosis (Bcl-2, Bax, pro-Caspase-3/9, and cleaved Caspase-3/9) and autophagy (microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, Beclin-1, and p62). Moreover, we examined the expression of ß-catenin and dissected the phosphorylation of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B (AKT). We found that H2O2 decreased the viability of PC12 cells while initiated apoptosis and autophagy processes. GTP-preincubated PC12 cells maintained the viability and resisted the apoptosis and autophagy induced by H2O2. Pointedly, GTP-pretreated PC12 cells showed an increase in MALAT1 after H2O2 stimulation. Of note, the protective effects of GTP were buffered in MALAT1-deficient cells in response to H2O2. The expression of ß-catenin and phosphorylation of PI3K and AKT were upregulated by GTP, while MALAT1 knockdown led to opposite results. To sum up, GTP protected PC12 cells from H2O2-induced damages by the upregulation of MALAT1. This process might be through activating Wnt/ß-catenin and PI3K/AKT signal pathways.


Assuntos
Peróxido de Hidrogênio/toxicidade , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , RNA Longo não Codificante/genética , Chá , Animais , Apoptose/efeitos dos fármacos , Inativação Gênica , Células PC12 , Ratos , Regulação para Cima/efeitos dos fármacos
14.
Nat Commun ; 10(1): 3896, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467270

RESUMO

Iron (Fe) is essential for life, but in excess can cause oxidative cytotoxicity through the generation of Fe-catalyzed reactive oxygen species. It is yet unknown which genes and mechanisms can provide Fe-toxicity tolerance. Here, we identify S-nitrosoglutathione-reductase (GSNOR) variants underlying a major quantitative locus for root tolerance to Fe-toxicity in Arabidopsis using genome-wide association studies and allelic complementation. These variants act largely through transcript level regulation. We further show that the elevated nitric oxide is essential for Fe-dependent redox toxicity. GSNOR maintains root meristem activity and prevents cell death via inhibiting Fe-dependent nitrosative and oxidative cytotoxicity. GSNOR is also required for root tolerance to Fe-toxicity throughout higher plants such as legumes and monocots, which exposes an opportunity to address crop production under high-Fe conditions using natural GSNOR variants. Overall, this study shows that genetic or chemical modulation of the nitric oxide pathway can broadly modify Fe-toxicity tolerance.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Tolerância a Medicamentos/fisiologia , Glutationa Redutase/metabolismo , Ferro/metabolismo , Ferro/toxicidade , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Morte Celular , Loci Gênicos , Estudo de Associação Genômica Ampla , Glutationa Redutase/genética , Haplótipos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Meristema/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/toxicidade , Nitrosação , Estresse Oxidativo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas
15.
Chem Biol Interact ; 311: 108776, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369745

RESUMO

Omeprazole (OM), a prototype proton pump inhibitor, oxidizes thiol groups and induces DNA damage. The aim of this study was to evaluate the oxidative effects of omeprazole and its interactions with ascorbic acid (AA, 50 µM) and retinol palmitate (RP) in proficient and deficient Saccharomyces cerevisiae strains, as well as levels of cytogenetic damage in Sarcoma 180 (S180) cells. Omeprazole was tested at concentrations of 10, 20 and 40 µg/mL, whereas H2O2 (10 mM), cyclophosphamide (20 mg/mL), and saline (0.9% NaCl solution) were employed as stressor, positive control, and negative control, respectively. Results revealed that omeprazole concentration-dependently induces oxidative effects in S. cerevisiae strains. However, omeprazole co-treated with ascorbic acid (50 µM) and retinol palmitate (100 IU) significantly modulated the oxidative damage inflected on the S. cerevisiae strains. Furthermore, omeprazole did not produce micronucleus formation and chromosomal bridges in S180 cells, but induced shoots. Significant increase in karyolysis and karyorrhexis were also observed with the omeprazole treated groups, which was modulated by co-treatment with ascorbic acid and retinol palmitate. Taken all together, it is suggested that ascorbic acid and retinol palmitate can substantially modulate the oxidative damage caused by omeprazole on the S. cerevisiae strains, however, much precaution is recommended with omeprazole and antioxidant co-treatment.


Assuntos
Ácido Ascórbico/farmacologia , Aberrações Cromossômicas/efeitos dos fármacos , Omeprazol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida/toxicidade , Diterpenos , Peróxido de Hidrogênio/toxicidade , Camundongos , Testes para Micronúcleos , Vitamina A/farmacologia
16.
Invest Ophthalmol Vis Sci ; 60(10): 3669-3679, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469894

RESUMO

Purpose: To investigate the presence and role of fibroblast senescence in the dynamic process of corneal wound healing involving stromal cell apoptosis, proliferation, and differentiation. Methods: An in vivo corneal wound healing model was performed using epithelial debridement in C57BL/6 mice. The corneas were stained using TUNEL, Ki67, and α-smooth muscle actin (α-SMA) as markers of apoptosis, proliferation, and myofibroblastic differentiation, respectively. Cellular senescence was confirmed by senescence-associated ß-galactosidase (SA-ß-gal) staining and P16Ink4a expression. Mitogenic response and gene expression were compared among normal fibroblasts, H2O2-induced senescent fibroblasts, and TGF-ß-induced myofibroblasts in vitro. The senescence was further detected in mouse models of corneal scarring, alkali burn, and penetrating keratoplasty (PKP). Results: The apoptosis and proliferation of corneal stromal cells were found to peak at 4 and 24 hours after epithelial debridement. Positive staining of SA-ß-gal was observed clearly in the anterior stromal cells at 3 to 5 days. The senescent cells displayed P16Ink4a+ vimentin+ α-SMA+, representing the major origin of activated corneal resident fibroblasts. Compared with normal fibroblasts and TGF-ß-induced myofibroblasts, H2O2-induced senescent fibroblasts showed a nonfibrogenic phenotype, including a reduced response to growth factor basic fibroblast growth factor (bFGF) or platelet-derived growth factor-BB (PDGF-BB), increased matrix metalloproteinase (MMP)1/3/13 expression, and decreased fibronectin and collagen I expression. Moreover, cellular senescence was commonly found in the mouse corneal scarring, alkali burn, and PKP models. Conclusions: Corneal epithelial debridement induced the senescence of corneal fibroblasts after apoptosis and proliferation. The senescent cells displayed a nonfibrogenic phenotype and may be involved in the self-limitation of corneal fibrosis.


Assuntos
Senescência Celular/fisiologia , Lesões da Córnea/fisiopatologia , Fibroblastos/citologia , Cicatrização/fisiologia , Actinas/metabolismo , Animais , Apoptose , Western Blotting , Proliferação de Células , Lesões da Córnea/metabolismo , Fibroblastos/metabolismo , Citometria de Fluxo , Peróxido de Hidrogênio/toxicidade , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Hidróxido de Sódio/toxicidade
17.
Mol Cell Biochem ; 462(1-2): 107-114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31463780

RESUMO

The aim of the work was to study the influence of vaspin on oxidative stress-induced apoptosis of mouse mesenchymal stem cells (MSCs). MSCs originated from bone marrow of C57BL/6 mouse were treated with vaspin and/or H2O2 in a dose-dependent manner. Cellular viability detected by CCK-8 and cell apoptosis studied by flow cytometry and TUNEL assay were observed in these cells. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, T-ERK1/2, p-ERK1/2, p38, p-p38, JNK, and p-JNK were tested by Western blot. Vaspin had no significant effect on cellular viability, but significantly reduced H2O2-induced apoptosis. Western blot assay showed that pretreatment with vaspin promoted the activation of p-p38. Inhibition of p38 by SB203580 suppressed the protective effect of vaspin on oxidative stress-induced apoptosis. Vaspin inhibits oxidative stress-induced apoptosis of MSCs via the activation of MAPK/p38 signaling pathway. These findings indicate that vaspin is prone to osteoporosis protection.


Assuntos
Adipocinas/metabolismo , Apoptose , Citoproteção , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/enzimologia , Células-Tronco Mesenquimais/patologia , Estresse Oxidativo , Serpinas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adipocinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serpinas/farmacologia
18.
Food Chem ; 299: 125165, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31306953

RESUMO

In the present study, the antioxidant hydrolysates obtained from watermelon seed protein (WSP) after divergent ultrasound and ultrafiltration treatment were studied. The results showed that the slit divergent ultrasound (SDU, 20/28 KHz) pretreatment had considerable influence on the structure and enzymatic efficiency of WSP. Besides, compared with hydrolysates without ultrasonic and ultrafiltration treatment, watermelon protein hydrolysates with molecular weight <1 kDa (WSPHs-I) showed the highest antioxidant activities and could protect RAW 264.7 cells from H2O2-induced oxidative stress damage via activating the Nrf2/HO-1 pathway. Interestingly, WSPHs-I had good stability against oxidation at temperature under 100 °C or in the acidic or neutral condition and still exhibited strong antioxidant activity after simulated gastrointestinal digestion. Taken together, SDU pretreatment could significantly increase the antioxidant activities and stability of WSPHs by improving the structure and facilitating enzymolysis of the WSP.


Assuntos
Antioxidantes/farmacologia , Citrullus/química , Proteínas de Plantas/química , Hidrolisados de Proteína/farmacologia , Ultrassom/métodos , Animais , Antioxidantes/química , Digestão/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Camundongos , Peso Molecular , Oxirredução , Proteínas de Plantas/farmacologia , Hidrolisados de Proteína/química , Estabilidade Proteica , Células RAW 264.7 , Proteínas de Armazenamento de Sementes/química , Sementes/química , Ultrafiltração
19.
Nutrients ; 11(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277394

RESUMO

This study investigated the protective effect and the molecular mechanism of piceatannol on hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell (ARPE-19) damage. Piceatannol treatment significantly inhibited H2O2-induced RPE cell death and reactive oxygen species (ROS) generation by 64.4% and 75.0%, respectively. Results of flow cytometry showed that H2O2-induced ARPE-19 cells apoptosis was ameliorated by piceatannol supplementation, along with decreased relative protein expressions of Bax/Bcl-2, Cleave-Caspase-3, and Cleave-PARP. Moreover, piceatannol treatment induced NF-E2-related factor 2 (Nrf2) signaling activation, which was evidenced by increased transcription of anti-oxidant genes, glutamate-cysteine ligase catalytic subunit (GCLc), SOD, and HO-1. Knockdown of Nrf2 through targeted siRNA alleviated piceatannol-mediated HO-1 transcription, and significantly abolished piceatannol-mediated cytoprotection. LY294002 (PI3K inhibitor) dramatically blocked piceatannol-mediated increasing of Nrf2 nuclear translocation, HO-1 expression, and cytoprotective activity, indicating the involvement of PI3K/Akt pathway in the cytoprotective effect of piceatannol. The results from this suggest the potential of piceatannol in reducing the risk of age-related macular degeneration.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estilbenos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Citoproteção , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Heme Oxigenase-1/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais
20.
Food Funct ; 10(7): 4231-4241, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31259337

RESUMO

The fruits of Lycium barbarum are considered medicinal foods with high nutritional value and bioactivity. In this study, we aimed to evaluate the effect of a crude L. barbarum polysaccharide (LBP) and two derived fractions, LBP-1 and LBP-2, on the lifespan of Drosophila melanogaster (fruit fly). The average lifespan of fruit flies was extended by supplementing their diet with either of the three LBP preparations. In vivo analysis of antioxidant activities detected increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) levels. Dietary LBP supplements significantly reduced the mortality rate of fruit flies induced by paraquat and hydrogen peroxide. Importantly, the strongest anti-aging activity was exhibited by the LBP-2 fraction, containing arabinogalactan with a molecular weight of 9 × 104 Da. Further studies showed that the anti-aging activity of LBP was, at least in part, mediated by an age-related signaling pathway (MAPK, TOR, S6K) and the expression of longevity genes (Hep, MTH, and Rpn11).


Assuntos
Drosophila melanogaster/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Longevidade/efeitos dos fármacos , Animais , Antioxidantes/análise , Catalase/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Endopeptidases/genética , Endopeptidases/metabolismo , Frutas/química , Regulação da Expressão Gênica , Peróxido de Hidrogênio/toxicidade , Malondialdeído/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Peso Molecular , Paraquat/toxicidade , Extratos Vegetais/farmacologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Superóxido Dismutase/metabolismo
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