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1.
Chemosphere ; 235: 1134-1145, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561304

RESUMO

Particulate matter (PM) from layer house has adverse effect on people and chicken respiratory health, which can further influence animal performance and reduce production efficiency. However, little study focus on the respiratory inflammation induced by PM2.5 from layer house and the underlying mechanism also unclear. In this study, human adenocarcinoma alveolar basal epithelial cells (A549 cell) was subjected to the PM2.5 from layer house to evaluate the inflammation reaction caused by PM2.5 and explore the role of Nrf2 and autophagy in regulating the inflammation. Results showed that the viability of A549 cell decreased in a time - and concentration - dependent manner after PM2.5 treatment. TNFα, IL6, and IL8 increased significantly treated with PM2.5 at 12 h. RNA sequencing indicated differentially expressed genes were enriched in immune system process, oxidative stress (OS), endoplasmic reticulum stress (ERS), and autophagy. Further studies showed TLR4 - NFκB p65 signal pathway involved in the inflammation reaction caused by PM2.5. The overexpression of Nrf2 decreased the level of TNFα, IL6, IL8 markedly as well as the level of NFκB p65 and NFκB pp65. OS and ERS were also limited under overactivation of Nrf2 in PM2.5 treated cells. Autophagy induced by PM2.5 promoted the inflammation through increasing the level of NFκB p65 and NFκB pp65. Autophagy deficient strengthened the expression of Nrf2. Collectively, our study revealed Nrf2 prevents inflammation caused by layer house PM2.5 stimulation, however, autophagy exerts a promotive role in TLR4 - NFκB p65 mediating inflammation in A549 cell.


Assuntos
Autofagia/fisiologia , Inflamação/etiologia , Fator 2 Relacionado a NF-E2/fisiologia , Material Particulado/efeitos adversos , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Células A549 , Animais , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/farmacologia , Estresse Oxidativo/genética , Transdução de Sinais
2.
Pestic Biochem Physiol ; 159: 1-8, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400771

RESUMO

We examined the molecular regulation of porphyrin biosynthesis and protective responses in transgenic rice (Oryza sativa) expressing Bradyrhizobium japonicum Fe-chelatase (BjFeCh) after treatment with acifluorfen (AF). During the photodynamic stress imposed by AF, transcript levels of BjFeCh in transgenic plants increased greatly; moreover, transcript levels of OsFeCh2 remained almost constant, whereas in wild type (WT) plants they were considerably down-regulated. In the heme branch, transgenic plants exhibited greater levels of OsFC and HO transcripts than WT plants in the untreated stems as well as in the AF-treated leaves and stems. Both WT and transgenic plants treated with AF substantially decreased transcript levels for all the genes in the chlorophyll branch, with less decline in transgenic plants. After AF treatment, ascorbate (Asc) content and the redox Asc state greatly decreased in leaves of WT plants; however, in transgenic plants both parameters remained constant in leaves and the Asc redox state increased by 20% in stems. In response to AF, the leaves of WT plants greatly up-regulated CatA, CatB, and GST compared to those of transgenic plants, whereas, in the stems, transgenic plants showed higher levels of CatA, CatC, APXb, BCH, and VDE. Photochemical quenching, qP, was considerably dropped by 31% and 18% in WT and transgenic plants, respectively in response to AF, whereas non-radiative energy dissipation through non-photochemical quenching increased by 77% and 38% in WT and transgenic plants, respectively. Transgenic plants treated with AF exhibited higher transcript levels of nucleus-encoded photosynthetic genes, Lhcb1 and Lhcb6, as well as levels of Lhcb6 protein compared to those of WT plants. Our study demonstrates that expression of BjFeCh in transgenic plants influences not only the regulation of porphyrin biosynthesis through maintaining higher levels of gene expression in the heme branch, but also the Asc redox function during photodynamic stress caused by AF.


Assuntos
Proteínas de Bactérias/metabolismo , Bradyrhizobium/enzimologia , Ferroquelatase/metabolismo , Nitrobenzoatos/farmacologia , Oryza/metabolismo , Porfirinas/biossíntese , Proteínas de Bactérias/genética , Ferroquelatase/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Plantas Geneticamente Modificadas
3.
Int J Nanomedicine ; 14: 4801-4816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308659

RESUMO

Background: Silver nanoparticles (AgNPs) inhibit the proliferation of various fungi; however, their mechanisms of action remain poorly understood. To better understand the inhibitory mechanisms, we focused on the early events elicited by 5 nm AgNPs in pathogenic Candida albicans and non-pathogenic Saccharomyces cerevisiae. Methods: The effect of 5 nm and 100 nm AgNPs on fungus cell proliferation was analyzed by growth kinetics monitoring and spot assay. We examined cell cycle progression, reactive oxygen species (ROS) production, and cell death using flow cytometry. Glucose uptake was assessed using tritium-labeled 2-deoxyglucose. Results: The growth of both C. albicans and S. cerevisiae was suppressed by treatment with 5 nm AgNPs but not with 100 nm AgNPs. In addition, 5 nm AgNPs induced cell cycle arrest and a reduction in glucose uptake in both fungi after 30 minutes of culture in a dose-dependent manner (P<0.05). However, in C. albicans only, an increase in ROS production was detected after exposure to 5 nm AgNPs. Concordantly, an ROS scavenger blocked the effect of 5 nm AgNPs on the cell cycle and glucose uptake in C. albicans only. Furthermore, the growth-inhibition effect of 5 nm AgNPs was not greater in S. cerevisiae mutant strains deficient in oxidative stress response genes than it was in wild type. Finally, 5 nm AgNPs together with a glycolysis inhibitor, 3-bromopyruvate, synergistically enhanced cell death in C. albicans (P<0.05) but not in S. cerevisiae. Conclusion: AgNPs exhibit antifungal activity in a manner that may or may not be ROS dependent, according to the fungal species. The combination of AgNPs with 3-bromopyruvate may be more useful against infection with C. albicans.


Assuntos
Candida albicans/citologia , Ciclo Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Piruvatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/citologia , Prata/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Depuradores de Radicais Livres/farmacologia , Fase G1/efeitos dos fármacos , Genes Fúngicos , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento
4.
BMC Infect Dis ; 19(1): 600, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288760

RESUMO

BACKGROUND: Oxidative stress plays a vital role in the pathogenesis of both Sickle Cell Disease (SCD) and Plasmodium falciparum malaria. However, there are limited studies on the effect of P. falciparum malaria infection on oxidative stress in SCD patients. METHODS: A cross-sectional study was undertaken to compare levels of biomarkers of oxidative stress in isolates from SCD patients with uncomplicated P.falciparum malaria. The biomarkers namely: malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were determined in plasma samples from SCD malaria positive, malaria positive, SCD malaria negative and healthy control participants. The genetic diversity of P.falciparum was determined by nested polymerase chain reaction of merozoite surface protein-2 (MSP-2) gene. RESULTS: Out of 207 participants, 54 (26%) were SCD malaria positive, 51 (24%) malaria positive, 51 (24%) SCD controls and 51 (24%) healthy control individuals. The mean concentration of MDA was significantly higher in SCD malaria positive than SCD controls (P < 0.0001). In contrast, the mean concentration of GSH (P < 0.0001) and GPx (P < 0.0001) were significantly lower in SCD malaria than SCD controls. Although not significantly different, the mean concentration of MDA was higher (P = 0.0478), but the geometric mean parasite density (P = 0.2430) and multiplicity of infection (P = 0.3478) were lower in SCD malaria samples than in malaria samples. The most prevalent MSP2 allelic family was IC3D7 in SCD malaria (72%) and Malaria (76%) samples. The biomarkers of oxidative stress were not significantly different between IC3D7 and FC27 allelic families of MSP2. CONCLUSION: We identified severe oxidative stress in Sickle cell disease patients with uncomplicated P.falciparum malaria.


Assuntos
Anemia Falciforme/diagnóstico , Malária Falciparum/diagnóstico , Estresse Oxidativo , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Antígenos de Protozoários/genética , Biomarcadores/metabolismo , Catalase/metabolismo , Estudos Transversais , Teste em Amostras de Sangue Seco , Feminino , Variação Genética , Genótipo , Glutationa/metabolismo , Humanos , Malária Falciparum/parasitologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/genética , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/genética , Índice de Gravidade de Doença , Uganda
5.
J Dairy Sci ; 102(9): 7684-7696, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31255276

RESUMO

Oxidative stress is the basic reason for aging and age-related diseases. In this study, we investigated the protective effect of 2 strains of lactic acid bacteria (LAB), Lactobacillus rhamnosus GG and L. plantarum J26, against oxidative stress in Caco-2 cells, and gave an overview of the mechanisms of lactic acid bacteria antioxidant activity using digital gene expression profiling. The 2 LAB strains provided significant protection against hydrogen peroxide (H2O2)-induced reduction in superoxide dismutase activity and increase in glutathione peroxidase activity in Caco-2 cells. However, inactive bacteria had little effect on alleviating oxidation stress in Caco-2 cells. Eight genes related to oxidative stress-FOSB, TNF, PPP1R15A, NUAK2, ATF3, TNFAIP3, EGR2, and FBN2-were significantly upregulated in H2O2-induced Caco-2 cells compared with untreated Caco-2 cells. After incubation of the H2O2-induced Caco-2 cells with L. rhamnosus GG and L. plantarum J26, 5 genes (TNF, EGR2, NUAK2, FBN2, and TNFAIP3) and 2 genes (NUAK2 and FBN2) were downregulated, respectively. In addition, the Kyoto Encyclopedia of Genes and Genomes indicated that some signaling pathways associated with inflammation, immune response, and apoptosis, such as Janus kinase/signal transducers and activators of transcription (Jak-STAT), mitogen-activated protein kinase (MAPK), nuclear factor-κB, and tumor necrosis factor, were all negatively modulated by the 2 strains, especially L. rhamnosus GG. In this paper, we reveal the mechanism of LAB in relieving oxidative stress and provide a theoretical basis for the rapid screening and evaluation of new LAB resources.


Assuntos
Enterócitos/metabolismo , Lactobacillus plantarum/fisiologia , Lactobacillus rhamnosus/fisiologia , Estresse Oxidativo/genética , Transcriptoma/genética , Animais , Apoptose/genética , Células CACO-2 , Enterócitos/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/fisiologia , Humanos , Peróxido de Hidrogênio/farmacologia , Imunidade/genética , Inflamação/genética , Probióticos/farmacologia
6.
Ecotoxicol Environ Saf ; 182: 109384, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31272023

RESUMO

Exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates link to oxidative stress and inflammatory response, which exert cellular aging. However, modification effect of seasonal factor on the association of PAHs or phthalates exposure with relative telomere length (RTL) or mitochondrial DNA copy number (mtDNA-CN) has remained unclear. In this pilot study, 106 subjects were from an urban population (n = 1240) who lived in the two districts in Wuhan city, China. Participants completed physical examinations and provided 191 blood samples for RTL and mtDNA-CN analysis and 627 urine samples for monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites measurements in the winter and summer seasons. We assessed the associations of urinary OH-PAHs or phthalates metabolites with RTL or mtDNA-CN by linear regression analysis and linear mixed-effect models. We found that urinary OH-PAHs were positively associated with mtDNA-CN at lag 2 day and 3-day moving average, but negatively related to RTL at lag 0, lag 1 and lag 2 day and 3-day moving average (p < 0.05). Urinary phthalate metabolites were negatively associated with mtDNA lag 0, lag 1 and lag 2 day and 3-day moving average, but positively related to RTL at lag 0 day (p < 0.05). Seasonal factor modified the association of urinary OH-PAHs with mtDNA-CN as well as urinary phthalate metabolites with RTL. In vitro experiment showed that under certain conditions, benzo[a]pyrene increased mtDNA-CN at 48 h and di (2-ethylhexyl) phthalate did RTL at 24 h in HepG2 cells. Seasonal variations in the metabolisms of PAHs or phthalates in human body may affect the relation of PAHs or phthalates exposure with cellular aging.


Assuntos
Senescência Celular/efeitos dos fármacos , Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/sangue , Ácidos Ftálicos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Telômero/efeitos dos fármacos , Adulto , Senescência Celular/genética , China , Células Hep G2 , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Ácidos Ftálicos/urina , Projetos Piloto , Hidrocarbonetos Policíclicos Aromáticos/urina , Estações do Ano , Adulto Jovem
7.
Ecotoxicol Environ Saf ; 182: 109388, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299477

RESUMO

Iron in excess can have toxic effects on living organisms. In China, the freshwater crayfish Procambarus clarkii is a source of aquatic food with high-quality protein and has significant commercial value. P. clarkii shows oxidative stress on exposure to heavy metals, and antioxidant enzymes, such as ubiquitination enzymes and proteasomes, play important roles in oxidative stress. To understand the antioxidant defense system of P. clarkii, we analyzed the hepatopancreas transcriptomes of P. clarkii after stimulation with FeCl3. In total, 5199 differentially expressed genes (DEGs) were identified (2747 upregulated and 2452 downregulated). GO analysis revealed that these DEGs belonged to 16 cellular component, 16 molecular function, and 19 biological process subcategories. A total of 1069 DEGs were classified into 25 categories by using COG. Some antioxidant defense pathways, such as "Ubiquitin mediated proteolysis" and "Glutathione metabolism," were identified using KEGG. In addition, quantitative real time-PCR (qRT-PCR) substantiated the up-regulation of a random selection of DEGs including antioxidant and immune defense genes. We obtained information for P. clarkii transcriptome databases and new insights into the responses of P. clarkii hepatopancreas to heavy metals.


Assuntos
Antioxidantes/metabolismo , Astacoidea/efeitos dos fármacos , Compostos Férricos/toxicidade , Hepatopâncreas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Astacoidea/genética , China , Perfilação da Expressão Gênica , Hepatopâncreas/metabolismo , Estresse Oxidativo/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real
8.
Ecotoxicol Environ Saf ; 182: 109453, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31349105

RESUMO

Telomeres are DNA-protein structures that protect chromosome ends from degradation and fusion, which are shortened by oxidative stress, for example air pollution including benzene, toluene, Coke Oven Emissions (COEs), and so on. As a biomarker of health and disease, telomere length is associated with cardiovascular, diabetes and cancers. The aim of this study was to estimate the effects of COEs exposure on telomere length and the benchmark dose (BMD) of COEs. A total of 542 coke oven workers and 235 healthy controls without exposure to toxicants were recruited. Quantitative PCR was used to determine the telomere length in human peripheral blood leukocytes DNA. Propensity scoring was used to match coke oven workers to healthy controls. Linear regression models and trend tests were used to the relationship between COEs exposure and telomere length. Telomere length in COEs exposed group 0.764 (0.536, 1.092) was significantly shorter than that in the control group 1.064(0.762, 1.438), (P < 0.001). There were significantly dose-response relationships between COEs exposure and telomere damage with telomere length as a biomarker. A BMDL value lower than the present occupational exposure limits (OELs) of COEs exposure was evaluated using the BMD approach in coke oven workers. Our results suggested that shorter telomere length is related to occupational exposure to COEs and the level of COEs exposure lower than the current national OELs in China and many other countries could induce telomere damage.


Assuntos
Poluentes Ocupacionais do Ar/análise , Coque/análise , Exposição Ocupacional/análise , Telômero/efeitos dos fármacos , Adolescente , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Benchmarking , Biomarcadores/análise , Estudos de Casos e Controles , China , Coque/toxicidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Telômero/ultraestrutura , Adulto Jovem
9.
Aquat Toxicol ; 213: 105213, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31200332

RESUMO

Atrazine is a widely used pesticide which acts as an endocrine disruptor in various organisms. The aim of this study was to investigate adverse effects of atrazine on life parameters, oxidative stress, and ecdysteroid biosynthetic pathway in the marine copepod Tigriopus japonicus. In T. japonicus, no mortality was shown in response to atrazine up to 20 mg/L in acute toxicity assessment. In nauplii, retardation in the growth and prolonged molting and metamorphosis resulted under chronic exposure of atrazine at 20 mg/L. In addition, body sizes of T. japonicus nauplii were significantly decreased (P < 0.01 in length and P < 0.001 in width) in response to 20 mg/L of atrazine. Furthermore, atrazine induced oxidative stress by the generation of reactive oxygen species at all concentrations compared to the control in the nauplii. Also, significant increase in glutathione-S transferase activity was observed in adult T. japonicus at low concentration of atrazine. To understand effects of atrazine on ecdysteroid biosynthetic pathway-involved genes (e.g., neverland, CYP307E1, CYP306A1, CYP302A1, CYP3022A1 [CYP315A1], CYP314A1, and CYP18D1) were examined with mRNA expressions of ecdysone receptor (EcR) and ultraspiracle (USP) in response to 20 mg/L atrazine in nauplii and adults. In the nauplii, these genes were significantly downregulated (P < 0.05) in response to atrazine, compared to the control but not in the adult T. japonicus. These results suggest that atrazine can interfere in vivo life parameters by oxidative stress-induced retrogression and ecdysteroid biosynthetic pathway in this species.


Assuntos
Organismos Aquáticos/metabolismo , Atrazina/toxicidade , Vias Biossintéticas/efeitos dos fármacos , Copépodes/efeitos dos fármacos , Ecdisteroides/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Animais , Organismos Aquáticos/efeitos dos fármacos , Organismos Aquáticos/genética , Atrazina/química , Vias Biossintéticas/genética , Tamanho Corporal/efeitos dos fármacos , Copépodes/genética , Copépodes/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/metabolismo , Estresse Oxidativo/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade
10.
DNA Cell Biol ; 38(8): 747-753, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31188020

RESUMO

Aberrant neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. While the genotoxic function of PMNs and its implications in carcinogenesis have been primarily associated with oxidative stress, recent work by Butin-Israeli and colleagues has defined a novel mechanism where PMN-derived microparticles through the delivery and activity of specific miRNAs promoted formation of double-strand breaks (DSBs), and in parallel, suppressed DSB repair through the downregulation of lamin B1 and Rad51. Respective downregulation of these two proteins compromised the nuclear envelope and high-fidelity repair by homologous recombination, increasing DSB accumulation and aneuploidy. This discovery defined a novel mode of action where PMN-mediated suppression of DSB repair leading to genomic instability in the injured mucosa may facilitate progression toward colorectal cancer.


Assuntos
Instabilidade Genômica , Doenças Inflamatórias Intestinais/tratamento farmacológico , Neutrófilos/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Quebras de DNA de Cadeia Dupla , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , MicroRNAs/metabolismo , Neutrófilos/fisiologia , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo
11.
BMC Bioinformatics ; 20(Suppl 12): 318, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31216986

RESUMO

BACKGROUND: Identification of motifs-recurrent and statistically significant patterns-in biological networks is the key to understand the design principles, and to infer governing mechanisms of biological systems. This, however, is a computationally challenging task. This task is further complicated as biological interactions depend on limited resources, i.e., a reaction takes place if the reactant molecule concentrations are above a certain threshold level. This biochemical property implies that network edges can participate in a limited number of motifs simultaneously. Existing motif counting methods ignore this problem. This simplification often leads to inaccurate motif counts (over- or under-estimates), and thus, wrong biological interpretations. RESULTS: In this paper, we develop a novel motif counting algorithm, Partially Overlapping MOtif Counting (POMOC), that considers capacity levels for all interactions in counting motifs. CONCLUSIONS: Our experiments on real and synthetic networks demonstrate that motif count using the POMOC method significantly differs from the existing motif counting approaches, and our method extends to large-scale biological networks in practical time. Our results also show that our method makes it possible to characterize the impact of different stress factors on cell's organization of network. In this regard, analysis of a S. cerevisiae transcriptional regulatory network using our method shows that oxidative stress is more disruptive to organization and abundance of motifs in this network than mutations of individual genes. Our analysis also suggests that by focusing on the edges that lead to variation in motif counts, our method can be used to find important genes, and to reveal subtle topological and functional differences of the biological networks under different cell states.


Assuntos
Redes Reguladoras de Genes/genética , Saccharomyces cerevisiae/genética , Algoritmos , Bases de Dados Genéticas , Genes Fúngicos , Modelos Biológicos , Estresse Oxidativo/genética
12.
BMC Plant Biol ; 19(1): 278, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238869

RESUMO

BACKGROUND: NAC (NAM, ATAF and CUC) transcriptional factors constitute a large family with more than 150 members in rice and several members of this family have been demonstrated to play crucial roles in rice abiotic stress response. In the present study, we report the function of a novel stress-responsive NAC gene, ONAC066, in rice drought and oxidative stress tolerance. RESULTS: ONAC066 was localized in nuclei of cells when transiently expressed in Nicotiana benthamiana and is a transcription activator with the binding ability to NAC recognition sequence (NACRS) and AtJUB1 binding site (JBS). Expression of ONAC066 was significantly induced by PEG, NaCl, H2O2 and abscisic acid (ABA). Overexpression of ONAC066 in transgenic rice improved drought and oxidative stress tolerance and increased ABA sensitivity, accompanied with decreased rate of water loss, increased contents of proline and soluble sugars, decreased accumulation of reactive oxygen species (ROS) and upregulated expression of stress-related genes under drought stress condition. By contrast, RNAi-mediated suppression of ONAC066 attenuated drought and oxidative stress tolerance and decreased ABA sensitivity, accompanied with increased rate of water loss, decreased contents of proline and soluble sugars, elevated accumulation of ROS and downregulated expression of stress-related genes under drought stress condition. Furthermore, yeast one hybrid and chromatin immunoprecipitation-PCR analyses revealed that ONAC066 bound directly to a JBS-like cis-elements in OsDREB2A promoter and activated the transcription of OsDREB2A. CONCLUSION: ONAC066 is a nucleus-localized transcription activator that can respond to multiple abiotic stress factors. Functional analyses using overexpression and RNAi-mediated suppression transgenic lines demonstrate that ONAC066 is a positive regulator of drought and oxidative stress tolerance in rice.


Assuntos
Secas , Oryza/genética , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Oryza/metabolismo , Estresse Oxidativo/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo
13.
Life Sci ; 232: 116526, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170418

RESUMO

Tumors and heart disease are two of the leading causes of human death. With the development of anti-cancer therapy, the survival rate of cancer patients has been significantly improved. But at the same time, the incidence of cardiovascular adverse events caused by cancer treatment has also been considerably increased, such as arrhythmia, left ventricular (LV) systolic and diastolic dysfunction, and even heart failure (HF), etc., which seriously affects the quality of life of cancer patients. More importantly, the occurrence of adverse events may lead to the adjustment or the cessation of anti-cancer treatment, which affects the survival rate of patients. Understanding the mechanism of cardiotoxicity (CTX) induced by antineoplastic drugs is the basis of adequate protection of the heart without impairing the efficacy of antineoplastic therapy. Based on current research, a large amount of evidence has shown that oxidative stress (OS) plays an essential role in CTX induced by antineoplastic drugs and participates in its toxic reaction directly and indirectly. Here, we will review the mechanism of action of OS in cardiac toxicity of antineoplastic drugs, to provide new ideas for researchers, and provide further guidance for clinical prevention and treatment of cardiac toxicity of anti-tumor drugs in the future.


Assuntos
Antineoplásicos/metabolismo , Cardiotoxicidade/prevenção & controle , Estresse Oxidativo/fisiologia , Antineoplásicos/efeitos adversos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Cardiotoxicidade/metabolismo , Coração/fisiopatologia , Cardiopatias/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Qualidade de Vida
14.
Environ Pollut ; 246: 955-962, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159145

RESUMO

Perfluorooctanoic acid (PFOA) toxicity is of considerable concern due to its wide application, environmental persistence, and bioaccumulation. In the current study, we used a scaffold-free three-dimensional (3D) spheroid model of mouse liver cells (AML12) to explore the toxicity of PFOA and emerging alternatives (HFPO-DA and PFO4DA). Comparing the short-term (24 and 72 h treatment) toxicity of PFOA between conventional 2D monolayer cells and 3D spheroids, we found that spheroids had higher EC50 values and lower ROS levels after treatment, indicating their greater resistance to PFOA. Cell viability (i.e., adenosine triphosphate (ATP) content and lactate dehydrogenase (LDH) leakage) and liver-specific function (i.e., albumin secretion) were stable in spheroids through 28 day of culture. However, under 100 and 200 µM-PFOA treatment for 28 day, ROS levels, LDH leakage, and caspase3/7 activity all increased significantly. As a sensitive parameter, ROS showed a significant increase at 21 day, even in the 50 µM-PFOA group. Consistent with the elevation of ROS and caspase3/7, the expressions of oxidative stress- and apoptosis-related genes, including Gsta2, Nqo1, Ho-1, caspase3, p53, and p21, were induced in dose- and time-dependent manners after PFOA exposure. The peroxisome proliferator-activated receptor alpha (PPARα) pathway was also activated after treatment, with significant induction of its target genes, Fabp4 and Scd1. Similar to PFOA, both HFPO-DA and PFO4DA activated the PPARα pathway, induced ROS levels, and initiated cell damage, though at a relatively lower extent than that of PFOA. Our results imply that the 3D spheroid model is a valuable tool in chronic toxicological studies.


Assuntos
Caprilatos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Fígado/efeitos dos fármacos , Modelos Biológicos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Caprilatos/química , Linhagem Celular , Poluentes Ambientais/química , Fluorcarbonetos/química , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , PPAR alfa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
15.
BMC Genomics ; 20(1): 460, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170930

RESUMO

BACKGROUND: Hibernation is a physiological state exploited by many animals exposed to prolonged adverse environmental conditions associated with winter. Large changes in metabolism and cellular function occur, with many stress response pathways modulated to tolerate physiological challenges that might otherwise be lethal. Many studies have sought to elucidate the molecular mechanisms of mammalian hibernation, but detailed analyses are lacking in reptiles. Here we examine gene expression in the Australian central bearded dragon (Pogona vitticeps) using mRNA-seq and label-free quantitative mass spectrometry in matched brain, heart and skeletal muscle samples from animals at late hibernation, 2 days post-arousal and 2 months post-arousal. RESULTS: We identified differentially expressed genes in all tissues between hibernation and post-arousal time points; with 4264 differentially expressed genes in brain, 5340 differentially expressed genes in heart, and 5587 differentially expressed genes in skeletal muscle. Furthermore, we identified 2482 differentially expressed genes across all tissues. Proteomic analysis identified 743 proteins (58 differentially expressed) in brain, 535 (57 differentially expressed) in heart, and 337 (36 differentially expressed) in skeletal muscle. Tissue-specific analyses revealed enrichment of protective mechanisms in all tissues, including neuroprotective pathways in brain, cardiac hypertrophic processes in heart, and atrophy protective pathways in skeletal muscle. In all tissues stress response pathways were induced during hibernation, as well as evidence for gene expression regulation at transcription, translation and post-translation. CONCLUSIONS: These results reveal critical stress response pathways and protective mechanisms that allow for maintenance of both tissue-specific function, and survival during hibernation in the central bearded dragon. Furthermore, we provide evidence for multiple levels of gene expression regulation during hibernation, particularly enrichment of miRNA-mediated translational repression machinery; a process that would allow for rapid and energy efficient reactivation of translation from mature mRNA molecules at arousal. This study is the first molecular investigation of its kind in a hibernating reptile, and identifies strategies not yet observed in other hibernators to cope stress associated with this remarkable state of metabolic depression.


Assuntos
Hibernação/genética , Répteis/genética , Adaptação Fisiológica , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Especificidade de Órgãos , Estresse Oxidativo/genética , Répteis/metabolismo , Répteis/fisiologia , Proteínas de Répteis/genética , Proteínas de Répteis/metabolismo
16.
BMC Res Notes ; 12(1): 250, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053168

RESUMO

OBJECTIVE: The objective of this experiment was to identify transcripts in baker's yeast (Saccharomyces cerevisiae) that could have originated from previously non-coding genomic regions, or de novo. We generated this data to be able to compare the transcriptomes of different species of Ascomycota. DATA DESCRIPTION: We generated high-depth RNA sequencing data for 11 species of yeast: Saccharomyces cerevisiae, Saccharomyces paradoxus, Saccharomyces mikatae, Saccharomyces kudriavzevii, Saccharomyces bayanus, Naumovia castelii, Kluyveromyces lactis, Lachancea waltii, Lachancea thermotolerans, Lachancea kluyveri, and Schizosaccharomyces pombe. Using RNA-Seq from yeast grown in rich and oxidative conditions we created genome-guided de novo assemblies of the transcriptomes for each species. We included synthetic spike-in transcripts in each sample to determine the lower limit of detection of the sequencing platform as well as the reliability of our de novo transcriptome assembly pipeline. We subsequently compared the de novo transcripts assemblies to the reference gene annotations and generated assemblies that comprised both annotated and novel transcripts.


Assuntos
Meios de Cultura/farmacologia , Estresse Oxidativo/genética , Transcriptoma/genética , Leveduras/crescimento & desenvolvimento , Leveduras/genética , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Leveduras/efeitos dos fármacos
17.
Ecotoxicol Environ Saf ; 180: 88-94, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078020

RESUMO

Cadmium (Cd) is a dangerous transition element that causes environmental and health problems due to its high mobility in the soil-plant system. In plants, Cd causes serious alterations in physiological processes, affecting different vital functions such as photosynthesis. Species such as Brassica juncea and Brassica rapa have been selected as suitable plants for phytoremediation purposes due to their ability to tolerate the toxic effect of heavy metals. In order to improve this strategy, techniques of plant mutagenesis such as TILLING (Targeting Induced Local Lessions in Genomes) have been employed. In the present work we studied the role of the HMA4 gene in the tolerance to Cd toxicity (100 µM CdCl2) using a TILLING mutant of B. rapa (BraA.hma4a-3). These mutant plants presented a lower biomass reduction and a higher Cd concentration in leaves. An increase in the GSH/GSSG ratio, in the content of photosynthetic pigments and a reduction of oxidative stress was observed, as well as a better photosynthetic index, confirming that BraA.hma4a-3 plants showed a higher tolerance to Cd. In conclusion, according to the results obtained in this work, BraA.hma4a-3 plants could be used for phytoremediation purposes of Cd contaminated soils.


Assuntos
Brassica rapa/efeitos dos fármacos , Cádmio/toxicidade , Genes de Plantas , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/toxicidade , Biodegradação Ambiental , Brassica rapa/genética , Cádmio/metabolismo , Mutação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fotossíntese/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Solo/química , Poluentes do Solo/metabolismo
18.
Medicine (Baltimore) ; 98(18): e15498, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045836

RESUMO

To perform a comprehensive analysis focusing on the biological functions and interactions of Kashin-Beck disease (KBD)-related genes to provide information towards understanding the pathogenesis of KBD.A retrospective, integrated bioinformatics analysis was designed and conducted. First, by reviewing the literature deposited in PubMed, we identified 922 genes genetically associated with KBD. Then, biological function and network analyses were conducted with Cytoscape software. Moreover, KBD specific molecular network analysis was conducted by Cytocluster using the Molecular Complex Detection Algorithm (MCODE).The biological function enrichment analysis suggested that collagen catabolic process, protein activation cascade, cellular response to growth factor stimulus, skeletal system development, and extrinsic apoptosis played important roles in KBD development. The apoptosis pathway, NF-kappa B signaling pathway, and the glutathione metabolism pathway were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in KBD occurrence and development. MCODE clusters showed that in top 3 clusters, 54 of KBD-related genes were included in the network and 110 candidate genes were discovered might be potentially related to KBD.The 110 candidate genes discovered in the current study may be related to the development of KBD. The expression changes of apoptosis and oxidative stress-related genes might serve as biomarkers for early diagnosis and treatment of KBD.


Assuntos
Apoptose/genética , Redes Reguladoras de Genes/genética , Doença de Kashin-Bek/genética , Estresse Oxidativo/genética , Transdução de Sinais/genética , Biologia Computacional , Humanos , Estudos Retrospectivos
19.
J Mol Histol ; 50(3): 239-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049798

RESUMO

Reduced expression of endothelial nitric oxide synthase (eNOS) is a hallmark of endothelial dysfunction in diabetes, which predisposes diabetic patients to numerous cardiovascular complications including blunted angiogenesis. The Krüppel-like factor (KLF) five has been implicated as a central regulator of cardiovascular remodeling, but its role in endothelial cells (ECs) remains poorly understood. We show here that expression of endothelial KLF5 was significantly increased in the ECs from mouse diabetes mellitus type 2 (T2DM) model, when compared to non-diabetic or T1DM mouse. KLF5 up-regulation by insulin was dependent on activation of multiple pathways, including mammalian target of rapamycin, oxidative stress and Protein kinase C pathways. Hyperinsulinemia-induced KLF5 inhibited endothelial function and migration, and thereby compromised in vitro and in vivo angiogenesis. Mechanistically, KLF5 acted in concert with the MTA1 coregulator to negatively regulate NOS3 transcription, thereby leading to the diminished eNOS levels in ECs. Conversely, potentiation of cGMP content (the essential downstream effector of eNOS signaling) by pharmacological approaches successfully rescued the endothelial proliferation and in vitro tube formation, in the HUVECs overexpressing the exogenous KLF5. Collectively, the available data suggest that the augmentation of endothelial KLF5 expression by hyperinsulinemia may represent a novel mechanism for negatively regulating eNOS expression, and may thus help to explain for the T2DM-related endothelial dysfunction at the transcriptional level.


Assuntos
Hiperinsulinismo/genética , Fatores de Transcrição Kruppel-Like/genética , Neovascularização Patológica/genética , Óxido Nítrico Sintase Tipo III/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperinsulinismo/patologia , Masculino , Camundongos , Estresse Oxidativo/genética , Proteína Quinase C/genética , Transdução de Sinais/genética
20.
Int J Mol Sci ; 20(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31085998

RESUMO

In this study, we provide experimental evidence that a maternally inherited polymorphism in the mitochondrial cytochrome b gene (mt-Cytb; m.15124A>G, Ile-Val) in mitochondrial complex III resulted in middle-aged obesity and higher susceptibility to diet-induced obesity, as well as age-related inflammatory disease, e.g., ulcerative dermatitis, in mice. As a consequence of the gene variation, we observed alterations in body composition, metabolism and mitochondrial functions, i.e., increased mitochondrial oxygen consumption rate and higher levels of reactive oxygen species, as well as in the commensal bacterial composition in the gut, with higher abundance of Proteobacteria in mice carrying the variant. These observations are in line with the previously described links of the mitochondrial complex III gene with obesity and metabolic diseases in humans. Given that these functional changes by the G variant at m.15124 in the mt-Cytb are already present in young mice that were kept under normal condition, it is plausible that the m.15124A>G variant is a disease susceptibility modifier to the diseases induced by additional stressors, i.e., dietary and/or aging stress, and that the variant results in the higher incidence of clinical diseases presentation in C57BL/6J-mt129S1/SvlmJ than C57BL/6J mice. Thus, mtDNA variants could be potential biomarkers to evaluate the healthspan.


Assuntos
DNA Mitocondrial/genética , Genes Mitocondriais/genética , Animais , Bacteroidetes/genética , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membranas Mitocondriais/metabolismo , Mutação/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Espécies Reativas de Oxigênio/metabolismo
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