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[PMID]:28968937
[Au] Autor:Olivares-Rubio HF; Salazar-Coria L; Nájera-Martínez M; Godínez-Ortega JL; Vega-López A
[Ad] Endereço:Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Toxicología Ambiental. Av. Wilfrido Massieu s/n, Unidad Profesional Zacatenco, México D.F. CP 07738, Mexico.
[Ti] Título:Lipid metabolism and pro-oxidant/antioxidant balance of Halamphora oceanica from the Gulf of Mexico exposed to water accommodated fraction of Maya crude oil.
[So] Source:Ecotoxicol Environ Saf;147:840-851, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Diatoms play key roles in primary production and carbon fixation at a global scale and in some cases these species live on marine ecosystems impacted by crude oil (CO) spills. Halamphora oceanica, a new diatom species from the Southwest of the Gulf of Mexico was isolated and cultured in the laboratory and was exposed to water accommodated fraction (WAF) of different Maya CO loads at 0.01, 0.1, 1 and 10g/L by 96h. A battery of biomarkers involved in oxidative stress (O •, H O , TBARS, ROOH, RC=O, SOD, CAT, GPx), biotransformation and conjugation (total CYP450 activity and GST) moreover fatty acid (FA) metabolism (FA levels, fatty-acid synthase and acyl-CoA oxidase) were measured. Obtained results suggest that increases of PAHs in the medium (below to EC ) acts as external forces able to turn-on regulatory mechanisms on H. oceanica involved in both, on the PAHs uptake and changing its aerobic metabolism to anaerobic metabolism. However, the growth of this microalgae species evaluated as chlorophyll "a" and pheophytin levels increased as the WAF concentration indicating that PAHs and other hydrosoluble hydrocarbons were used as carbon and energy sources by unidentified enzymes not evaluated in the current study. Our hypothesis was also corroborated by IBRv2. In the current study, we suppose the change from aerobic to anaerobic metabolism as a strategy for Halamphora oceanica survival exposed to petroleum hydrocarbons.
[Mh] Termos MeSH primário: Antioxidantes/metabolismo
Diatomáceas/efeitos dos fármacos
Metabolismo dos Lipídeos/efeitos dos fármacos
Oxidantes/metabolismo
Petróleo/toxicidade
Hidrocarbonetos Aromáticos Policíclicos/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Diatomáceas/metabolismo
Monitoramento Ambiental
Golfo do México
Estresse Oxidativo/efeitos dos fármacos
Petróleo/análise
Hidrocarbonetos Aromáticos Policíclicos/análise
Água do Mar/química
Poluentes Químicos da Água/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biomarkers); 0 (Oxidants); 0 (Petroleum); 0 (Polycyclic Aromatic Hydrocarbons); 0 (Water Pollutants, Chemical)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


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[PMID]:29478660
[Au] Autor:Li X; Huang Y; Liu HW; Wu C; Bi W; Yuan Y; Liu X
[Ad] Endereço:School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
[Ti] Título:Simultaneous Fe(III) reduction and ammonia oxidation process in Anammox sludge.
[So] Source:J Environ Sci (China);64:42-50, 2018 Feb.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In recent years, there have been a number of reports on the phenomenon in which ferric iron (Fe(III)) is reduced to ferrous iron [Fe(II)] in anaerobic environments, accompanied by simultaneous oxidation of ammonia to NO , NO , or N However, studies on the relevant reaction characteristics and mechanisms are rare. Recently, in research on the effect of Fe(III) on the activity of Anammox sludge, excess ammonia oxidization has also been found. Hence, in the present study, Fe(III) was used to serve as the electron acceptor instead of NO , and the feasibility and characteristics of Anammox coupled to Fe(III) reduction (termed Feammox) were investigated. After 160days of cultivation, the conversion rate of ammonia in the reactor was above 80%, accompanied by the production of a large amount of NO and a small amount of NO . The total nitrogen removal rate was up to 71.8%. Furthermore, quantities of Fe(II) were detected in the sludge fluorescence in situ hybridization (FISH) and denaturated gradient gel electrophoresis (DGGE) analyses further revealed that in the sludge, some Anammox bacteria were retained, and some microbes were enriched during the acclimatization process. We thus deduced that in Anammox sludge, Fe(III) reduction takes place together with ammonia oxidation to NO and NO along with the Anammox process.
[Mh] Termos MeSH primário: Amônia/química
Ferro/química
Esgotos/microbiologia
[Mh] Termos MeSH secundário: Aclimatação
Amônia/metabolismo
Respiração Celular
Crescimento Quimioautotrófico
Eletroforese em Gel de Gradiente Desnaturante
Meio Ambiente
Compostos Férricos
Hibridização in Situ Fluorescente
Ferro/metabolismo
Nitrogênio
Oxidantes
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ferric Compounds); 0 (Oxidants); 0 (Sewage); 7664-41-7 (Ammonia); E1UOL152H7 (Iron); N762921K75 (Nitrogen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180227
[St] Status:MEDLINE


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[PMID]:28460761
[Au] Autor:Samarghandian S; Azimi-Nezhad M; Farkhondeh T
[Ad] Endereço:Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. Electronic address: samarghandians@mums.ac.ir.
[Ti] Título:Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats.
[So] Source:Indian Heart J;69(2):151-159, 2017 Mar - Apr.
[Is] ISSN:0019-4832
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Crocus sativus L. (saffron) has many biological effects such as antioxidant property. The present study investigated the immunomodulatory effects of the aqueous saffron extract on streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three saffron extract-treated diabetic groups. Diabetes was induced by STZ in rats. Saffron was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays and the abdominal aorta was removed for detecting the inflammatory cytokines expression. RESULTS: We found that saffron decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (p<0.01) and increased glutathione level, catalase, and superoxide dismutase activities in the saffron-treated diabetic groups compared with the untreated groups, in a dose dependent manner (p<0.05, p<0.01, p<0.001). On the other hand, saffron-treated diabetic rats inhibited the expression of inflammatory cytokines in the abdominal aorta versus the untreated diabetic rats. CONCLUSION: Our results validate the use of saffron as a treatment against diabetes mellitus and its vascular complications.
[Mh] Termos MeSH primário: Antioxidantes/uso terapêutico
Crocus
Diabetes Mellitus Experimental/tratamento farmacológico
Imunomodulação
Lipídeos/sangue
Oxidantes/sangue
Estresse Oxidativo/efeitos dos fármacos
Extratos Vegetais/uso terapêutico
Espécies Reativas de Oxigênio/sangue
[Mh] Termos MeSH secundário: Animais
Glicemia/metabolismo
Diabetes Mellitus Experimental/sangue
Diabetes Mellitus Experimental/imunologia
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Blood Glucose); 0 (Lipids); 0 (Oxidants); 0 (Plant Extracts); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29343728
[Au] Autor:Carroll B; Otten EG; Manni D; Stefanatos R; Menzies FM; Smith GR; Jurk D; Kenneth N; Wilkinson S; Passos JF; Attems J; Veal EA; Teyssou E; Seilhean D; Millecamps S; Eskelinen EL; Bronowska AK; Rubinsztein DC; Sanz A; Korolchuk VI
[Ad] Endereço:Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University Institute for Ageing (NUIA), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
[Ti] Título:Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis.
[So] Source:Nat Commun;9(1):256, 2018 01 17.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.
[Mh] Termos MeSH primário: Autofagia
Proteostase
Espécies Reativas de Oxigênio/metabolismo
Proteína Sequestossoma-1/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Drosophila melanogaster/citologia
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Células HEK293
Células HeLa
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Camundongos Knockout
Oxidantes/farmacologia
Oxirredução
Homologia de Sequência de Aminoácidos
Proteína Sequestossoma-1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oxidants); 0 (Reactive Oxygen Species); 0 (Sequestosome-1 Protein); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02746-z


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[PMID]:29175419
[Au] Autor:Zhang Y; Igwe OJ
[Ad] Endereço:University of Missouri-Kansas City, School of Pharmacy, Division of Pharmacology & Toxicology, 2464 Charlotte Street, Kansas City, MO 64108, USA. Electronic address: yzqh9@mail.umkc.edu.
[Ti] Título:Exogenous oxidants activate nuclear factor kappa B through Toll-like receptor 4 stimulation to maintain inflammatory phenotype in macrophage.
[So] Source:Biochem Pharmacol;147:104-118, 2018 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Disturbances in redox equilibrium in tissue can lead to inflammatory state, which is a mediatory factor in many human diseases. The mechanism(s) by which exogenous oxidants may activate an inflammatory response is not fully understood. Emerging evidence suggests that oxidant-induced Toll-like receptor 4 (TLR4) activation plays a major role in "sterile" inflammation. In the present study, we used murine macrophage RAW-Blue cells, which are chromosomally integrated with secreted embryonic alkaline phosphatase (SEAP) inducible by NF-κB. We confirmed the expression of TLR4 mRNA and protein in RAW-Blue cells by RT-PCR and Western blot, respectively. We showed that oxidants increased intracellular reactive oxygen species production and lipid peroxidation, which resulted in decreased intracellular total antioxidant capacity. Consistent with the actions of TLR4-specific agonist LPS-EK, exogenous oxidants increased transcriptional activity of NF-κB p65 with subsequent release of NF-κB reporter gene SEAP. These effects were blocked by pretreatment with TLR4 neutralizing pAb and TLR4 signaling inhibitor CLI-095. In addition, oxidants decreased the expression of IκBα with enhanced phosphorylation at the Tyr42 residue. Finally, oxidants and LPS-EK increased TNFα production, but did not affect IL-10 production, which may cause imbalance between pro- and anti-inflammatory processes, which CLI-095 inhibited. For biological relevance, we confirmed that oxidants increased release of TNFα and IL-6 in primary macrophages derived from TLR4-WT and TLR4-KO mice. Our results support the involvement of TLR4 mediated oxidant-induced inflammatory phenotype through NF-κB activation in macrophages. Thus exogenous oxidants may play a role in activating inflammatory phenotypes that propagate and maintain chronic disease states.
[Mh] Termos MeSH primário: Macrófagos/metabolismo
NF-kappa B/metabolismo
Oxidantes/farmacologia
Fenótipo
Receptor 4 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Linhagem Celular
Relação Dose-Resposta a Droga
Mediadores da Inflamação/metabolismo
Macrófagos/efeitos dos fármacos
Camundongos
Camundongos Knockout
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antioxidants); 0 (Inflammation Mediators); 0 (NF-kappa B); 0 (Oxidants); 0 (Reactive Oxygen Species); 0 (Toll-Like Receptor 4)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:29223100
[Au] Autor:Deck LM; Hunsaker LA; Vander Jagt TA; Whalen LJ; Royer RE; Vander Jagt DL
[Ad] Endereço:Department of Chemistry and Chemical Biology, University of New Mexico, MSC03 2060, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: ldeck@unm.edu.
[Ti] Título:Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.
[So] Source:Eur J Med Chem;143:854-865, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
[Mh] Termos MeSH primário: Curcumina/farmacologia
Cetonas/farmacologia
Fator 2 Relacionado a NF-E2/antagonistas & inibidores
Oxidantes/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Curcumina/análogos & derivados
Curcumina/química
Relação Dose-Resposta a Droga
Células Hep G2
Seres Humanos
Cetonas/química
Estrutura Molecular
Fator 2 Relacionado a NF-E2/metabolismo
Oxidantes/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ketones); 0 (NF-E2-Related Factor 2); 0 (NFE2L2 protein, human); 0 (Oxidants); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE


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[PMID]:27779338
[Au] Autor:Annese C; D'Accolti L; Fusco C; Licini G; Zonta C
[Ad] Endereço:CNR-ICCOM, UOS Bari, Via Orabona 4, 70126, Bari, Italy.
[Ti] Título:Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N-H versus C-H Switch in the Oxidation of Lactams by Dioxirans.
[So] Source:Chemistry;23(2):259-262, 2017 01 05.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Dioxiranes are powerful oxidants that can act via two different mechanisms: 1) homolytic (H abstraction and oxygen rebound) and 2) heterolytic (electrophilic oxidation). So far, it has been reported that the nature of the substrate dictates the reaction mode independently from the dioxirane employed. Herein, we report an unprecedented case in which the nature of the dioxirane rules the oxidation chemoselectivity. In particular, a switch from C-H to N-H oxidation is observed in the oxidation of lactams moving from dimethyl dioxirane (DDO) to methyl(trifluoromethyl)dioxirane (TFDO). A physical organic chemistry study, which combines the oxidation with two other dioxiranes methyl(fluoromethyl)dioxirane, MFDO, and methyl(difluoromethyl)dioxirane, DFDO, with computational studies, points to a diverse ability of the dioxiranes to either stabilize the homo or the heterolytic pathway.
[Mh] Termos MeSH primário: Compostos de Epóxi/química
Lactamas/química
Oxidantes/química
[Mh] Termos MeSH secundário: Halogenação
Metilação
Oxirredução
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Epoxy Compounds); 0 (Lactams); 0 (Oxidants); 157-26-6 (dioxirane)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201604507


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[PMID]:28873576
[Au] Autor:Pohl F; Goua M; Bermano G; Russell WR; Scobbie L; Maciel P; Kong Thoo Lin P
[Ad] Endereço:School of Pharmacy and Life Science, Robert Gordon University, Aberdeen AB10 1GJ, Scotland, United Kingdom.
[Ti] Título:Revalorisation of rapeseed pomace extracts: An in vitro study into its anti-oxidant and DNA protective properties.
[So] Source:Food Chem;239:323-332, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rapeseed pomace (RSP) is a waste product obtained after edible oil production from Brassica napus. Analysis of ubiquitous secondary metabolites in RSP samples (two breeds, harvested in 2012/2014 respectively from North East of Scotland) and their ethanol/water (95:5) Soxhlet extracts were carried out. Soxhlet extraction of the RSP (petroleum ether followed by 95% ethanol) gave a solid extract. LC-MS/MS data of the extracts revealed several secondary metabolites, with Sinapic acid being the most abundant. Strong antioxidant activities of the Soxhlet extracts were confirmed from the results obtained in the FRAP, DPPH and ORAC assays. Furthermore, for the very first time, RSP extracts (13.9µg/ml) provided complete DNA protection, from oxidative stress induced by AAPH (3.5mM). Therefore the strong antioxidant and DNA protecting properties demonstrated by the RSP extracts in this study warrants further investigation for their revalorisation and potential use as reliable source of antioxidants in different food applications.
[Mh] Termos MeSH primário: Brassica rapa
[Mh] Termos MeSH secundário: Antioxidantes
DNA de Plantas
Oxidantes
Extratos Vegetais
Sementes
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (DNA, Plant); 0 (Oxidants); 0 (Plant Extracts)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE


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[PMID]:28892096
[Au] Autor:Loarca L; De Assuncao TM; Jalan-Sakrikar N; Bronk S; Krishnan A; Huang B; Morton L; Trussoni C; Bonilla LM; Krueger E; O'Hara S; Splinter P; Shi G; Pisarello MJL; Gores GJ; Huebert RC; LaRusso NF
[Ad] Endereço:Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
[Ti] Título:Development and characterization of cholangioids from normal and diseased human cholangiocytes as an in vitro model to study primary sclerosing cholangitis.
[So] Source:Lab Invest;97(11):1385-1396, 2017 Nov.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitro models. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients. In 3D culture, NHCs formed spheroids of ~5000 cells with a central lumen of ~150 µm. By confocal microscopy and western blot, cholangioids retained expression of cholangiocyte proteins (cytokeratin 7/19) and markers of epithelial polarity (secretin receptor and GM130). Cholangioids are functionally active, and upon secretin stimulation, luminal size increased by ~80%. Cholangioids exposed to hydrogen peroxide exhibited cellular senescence and the senescence-associated secretory phenotype (SASP; increased IL-6, p21, SA-ß-Gal, yH2A.x and p16 expression). Furthermore, cholangioids derived from NHC-sen or PSC patients were smaller and had slower growth than the controls. When co-cultured with THP-1 macrophages, the number of macrophages associated with NHC-sen or PSC cholangioids was five- to seven-fold greater compared to co-culture with non-senescent NHC. We observed that NHC-sen and PSC cholangioids release greater number of extracellular vesicles (EVs) compared to controls. Moreover, conditioned media from NHC-sen cholangioids resulted in an ~2-fold increase in macrophage migration. In summary, we developed a method to generate normal and diseased cholangioids, characterized them morphologically and functionally, showed that they can be induced to senescence and SASP, and demonstrated both EV release and macrophage attraction. This novel model mimics several features of PSC, and thus will be useful for studying the pathogenesis of PSC and potentially identifying new therapeutic targets.
[Mh] Termos MeSH primário: Ductos Biliares/patologia
Colangite Esclerosante/patologia
Esferoides Celulares/patologia
[Mh] Termos MeSH secundário: Autoantígenos/metabolismo
Ductos Biliares/efeitos dos fármacos
Ductos Biliares/metabolismo
Ductos Biliares/ultraestrutura
Biomarcadores/metabolismo
Linhagem Celular
Células Cultivadas
Senescência Celular/efeitos dos fármacos
Colangite Esclerosante/imunologia
Colangite Esclerosante/metabolismo
Técnicas de Cocultura
Meios de Cultivo Condicionados
Vesículas Extracelulares/efeitos dos fármacos
Vesículas Extracelulares/metabolismo
Vesículas Extracelulares/patologia
Vesículas Extracelulares/ultraestrutura
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Peróxido de Hidrogênio/toxicidade
Queratina-19/metabolismo
Queratina-7/metabolismo
Ativação de Macrófagos
Macrófagos/citologia
Macrófagos/imunologia
Proteínas de Membrana/metabolismo
Microscopia Eletrônica de Transmissão
Corpos Multivesiculares/efeitos dos fármacos
Corpos Multivesiculares/metabolismo
Corpos Multivesiculares/patologia
Corpos Multivesiculares/ultraestrutura
Oxidantes/toxicidade
Receptores Acoplados a Proteínas-G/metabolismo
Receptores dos Hormônios Gastrointestinais/metabolismo
Esferoides Celulares/efeitos dos fármacos
Esferoides Celulares/metabolismo
Esferoides Celulares/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantigens); 0 (Biomarkers); 0 (Culture Media, Conditioned); 0 (Golgin subfamily A member 2); 0 (KRT7 protein, human); 0 (Keratin-19); 0 (Keratin-7); 0 (Membrane Proteins); 0 (Oxidants); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Gastrointestinal Hormone); 0 (secretin receptor); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2017.63


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[PMID]:28890133
[Au] Autor:Nguyen HA; El Khoury T; Guiral S; Laaberki MH; Candusso MP; Galisson F; Foucher AE; Kesraoui S; Ballut L; Vallet S; Orelle C; Zucchini L; Martin J; Page A; Attieh J; Aghajari N; Grangeasse C; Jault JM
[Ad] Endereço:Institut de Biologie Structurale, Université Joseph Fourier Grenoble 1, UMR5075 CNRS/CEA/UJF, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
[Ti] Título:Expanding the Kinome World: A New Protein Kinase Family Widely Conserved in Bacteria.
[So] Source:J Mol Biol;429(20):3056-3074, 2017 Oct 13.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Fine tuning of signaling pathways is essential for cells to cope with sudden environmental variations. This delicate balance is maintained in particular by protein kinases that control the activity of target proteins by reversible phosphorylation. In addition to homologous eukaryotic enzymes, bacteria have evolved some specific Ser/Thr/Tyr protein kinases without any structural resemblance to their eukaryotic counterparts. Here, we show that a previously identified family of ATPases, broadly conserved among bacteria, is in fact a new family of protein kinases with a Ser/Thr/Tyr kinase activity. A prototypic member of this family, YdiB from Bacillus subtilis, is able to autophosphorylate and to phosphorylate a surrogate substrate, the myelin basic protein. Two crystal structures of YdiB were solved (1.8 and 2.0Å) that display a unique ATP-binding fold unrelated to known protein kinases, although a conserved HxD motif is reminiscent of that found in Hanks-type protein kinases. The effect of mutations of conserved residues further highlights the unique nature of this new protein kinase family that we name ubiquitous bacterial kinase. We investigated the cellular role of YdiB and showed that a ∆ydiB mutant was more sensitive to paraquat treatment than the wild type, with ~13% of cells with an aberrant morphology. In addition, YdiE, which is known to participate with both YdiC and YdiB in an essential chemical modification of some specific tRNAs, is phosphorylated in vitro by YdiB. These results expand the boundaries of the bacterial kinome and support the involvement of YdiB in protein translation and resistance to oxidative stress in B. subtilis.
[Mh] Termos MeSH primário: Bacillus subtilis/enzimologia
Bacillus subtilis/genética
Proteínas Quinases/química
Proteínas Quinases/genética
[Mh] Termos MeSH secundário: Bacillus subtilis/citologia
Bacillus subtilis/efeitos dos fármacos
Cristalografia por Raios X
Deleção de Genes
Oxidantes/toxicidade
Estresse Oxidativo
Paraquat/toxicidade
Fosforilação
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oxidants); EC 2.7.- (Protein Kinases); PLG39H7695 (Paraquat)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE



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