Base de dados : MEDLINE
Pesquisa : G02.111.165 [Categoria DeCS]
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  1 / 5778 MEDLINE  
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[PMID]:28467092
[Au] Autor:Wu M; Ye H; Shao C; Zheng X; Li Q; Wang L; Zhao M; Lu G; Chen B; Zhang J; Wang Y; Wang G; Hao H
[Ad] Endereço:Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines and ‡School of Pharmacy, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 210009, China.
[Ti] Título:Metabolomics-Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between Senescence and Apoptosis.
[So] Source:J Proteome Res;16(6):2250-2261, 2017 Jun 02.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Apoptosis and senescence are two types of cell fates in response to chemotherapy. Besides canonical pathways that mediate cell fates, cancer cell metabolism has been revealed as a crucial factor affecting cell fate decisions and thus represents a new target for antitumor therapy. Therefore, a comprehensive description of metabolic pathways underlying cell senescence and apoptosis in response to chemotherapy is highly demanded for therapeutic exploitation of both processes. Herein we employed a metabolomics-proteomics combined approach to identify metabolism-associated molecular events that mediate cellular responses to senescence and apoptosis using doxorubicin-treated human breast cancer cells MCF7 as models. Such biomics approach revealed that tricarboxylic acid cycle, pentose phosphate pathway, and nucleotide synthesis pathways were significantly upregulated in the senescent model, whereas fatty acid synthesis was reduced. In apoptotic cells, an overall reduced activity of major metabolic pathways was observed except for the arginine and proline pathway. Combinatorially, these data show the utility of biomics in exploring biochemical mechanism-based differences between apoptosis and senescence and reveal an unprecedented finding of the metabolic events that were induced for survival by facilitating ROS elimination and DNA damage repair in senescent cells, while they were downregulated in apoptotic cells when DNA damage was irreparable.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Senescência Celular/efeitos dos fármacos
Redes e Vias Metabólicas/efeitos dos fármacos
Metabolômica/métodos
Proteômica/métodos
[Mh] Termos MeSH secundário: Ciclo do Ácido Cítrico
Dano ao DNA
Doxorrubicina/farmacologia
Doxorrubicina/uso terapêutico
Ácidos Graxos/biossíntese
Seres Humanos
Células MCF-7
Nucleotídeos/biossíntese
Via de Pentose Fosfato
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Nucleotides); 0 (Reactive Oxygen Species); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.7b00111


  2 / 5778 MEDLINE  
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[PMID]:28453233
[Au] Autor:Huang YP; Chang NW
[Ad] Endereço:Department of Physiology, College of Medicine, China Medical University, Taichung, Taiwan.
[Ti] Título:Proteomic analysis of oral cancer reveals new potential therapeutic targets involved in the Warburg effect.
[So] Source:Clin Exp Pharmacol Physiol;44(8):880-887, 2017 Aug.
[Is] ISSN:1440-1681
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to disrupt tumour metabolism and to promote anticancer activity through interfering with the Warburg effect. This study is to investigate whether Warburg effect-related proteins also could be identified in oral tumour lesions and to explore the functional significance of PPARα in metabolic shift. Five pairs of tongue tumour tissues and adjacent reference tissues obtained from 4-NQO/arecoline induced mouse model were analyzed by 2-d-gel-electrophoresis and LC-MS. Further, the hexokinase II level, pyruvate dehydrogenase (PDH) activity, and metabolites of glycolysis and TCA cycle were all examined in order to validate the effect of PPARα on metabolic shift. Changes in protein expression levels revealed that seven proteins, which were involved in glycolysis, the tricarboxylic acid cycle, and the respiratory chain, were down-regulated in tumour tissues. We found that activation of PPARα through fenofibrate could inhibit oral cancer cell growth and switch the way of energy production from the Warburg effect to oxidative phosphorylation. Fenofibrate induced a reduction of hexokinase II protein levels, increases in PDH activity and metabolites of the TCA cycle, and an impairment of ATP production. These findings suggested that activation of the PPARα to reprogram the metabolic pathway might impair the Warburg effect and trigger cancer cell death. The study provides a novel view of changes in protein expression profiles involved in the Warburg effect during oral tumourigenesis. Activation of the PPARα to impair the Warburg effect might offer a new strategy for oral cancer treatment.
[Mh] Termos MeSH primário: Terapia de Alvo Molecular
Neoplasias Bucais/tratamento farmacológico
Neoplasias Bucais/metabolismo
Proteômica
[Mh] Termos MeSH secundário: Animais
Ciclo do Ácido Cítrico/efeitos dos fármacos
Glicólise/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Neoplasias Bucais/patologia
Fosforilação Oxidativa/efeitos dos fármacos
PPAR alfa/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PPAR alpha)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/1440-1681.12774


  3 / 5778 MEDLINE  
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[PMID]:29416026
[Au] Autor:Wang YQ; Wang HL; Xu J; Tan J; Fu LN; Wang JL; Zou TH; Sun DF; Gao QY; Chen YX; Fang JY
[Ad] Endereço:Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China.
[Ti] Título:Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner.
[So] Source:Nat Commun;9(1):545, 2018 02 07.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
[Mh] Termos MeSH primário: Carcinogênese/metabolismo
Neoplasias Colorretais/metabolismo
Regulação Neoplásica da Expressão Gênica/fisiologia
Glutamato Desidrogenase/metabolismo
Glutamina/metabolismo
Sirtuínas/metabolismo
[Mh] Termos MeSH secundário: Proliferação Celular
Ciclo do Ácido Cítrico/fisiologia
Regulação Enzimológica da Expressão Gênica/fisiologia
Glutamato Desidrogenase/genética
Células HCT116
Seres Humanos
Interferência de RNA
Sirtuínas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0RH81L854J (Glutamine); EC 1.4.1.2 (Glutamate Dehydrogenase); EC 1.4.1.3 (GLUD1 protein, human); EC 3.5.1.- (SIRT5 protein, human); EC 3.5.1.- (Sirtuins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-02951-4


  4 / 5778 MEDLINE  
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[PMID]:28470848
[Au] Autor:Camprubi E; Jordan SF; Vasiliadou R; Lane N
[Ad] Endereço:Department of Genetics, Evolution and Environment, University College London, London, UK.
[Ti] Título:Iron catalysis at the origin of life.
[So] Source:IUBMB Life;69(6):373-381, 2017 06.
[Is] ISSN:1521-6551
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Iron-sulphur proteins are ancient and drive fundamental processes in cells, notably electron transfer and CO fixation. Iron-sulphur minerals with equivalent structures could have played a key role in the origin of life. However, the 'iron-sulphur world' hypothesis has had a mixed reception, with questions raised especially about the feasibility of a pyrites-pulled reverse Krebs cycle. Phylogenetics suggests that the earliest cells drove carbon and energy metabolism via the acetyl CoA pathway, which is also replete in Fe(Ni)S proteins. Deep differences between bacteria and archaea in this pathway obscure the ancestral state. These differences make sense if early cells depended on natural proton gradients in alkaline hydrothermal vents. If so, the acetyl CoA pathway diverged with the origins of active ion pumping, and ancestral CO fixation might have been equivalent to methanogens, which depend on a membrane-bound NiFe hydrogenase, energy converting hydrogenase. This uses the proton-motive force to reduce ferredoxin, thence CO . The mechanism suggests that pH could modulate reduction potential at the active site of the enzyme, facilitating the difficult reduction of CO by H . This mechanism could be generalised under abiotic conditions so that steep pH differences across semi-conducting Fe(Ni)S barriers drives not just the first steps of CO fixation to C1 and C2 organics such as CO, CH SH and CH COSH, but a series of similar carbonylation and hydrogenation reactions to form longer chain carboxylic acids such as pyruvate, oxaloacetate and α-ketoglutarate, as in the incomplete reverse Krebs cycle found in methanogens. We suggest that the closure of a complete reverse Krebs cycle, by regenerating acetyl CoA directly, displaced the acetyl CoA pathway from many modern groups. A later reliance on acetyl CoA and ATP eliminated the need for the proton-motive force to drive most steps of the reverse Krebs cycle. © 2017 IUBMB Life, 69(6):373-381, 2017.
[Mh] Termos MeSH primário: Acetilcoenzima A/química
Ferredoxinas/química
Proteínas com Ferro-Enxofre/química
Ferro/química
Origem da Vida
[Mh] Termos MeSH secundário: Acetilcoenzima A/metabolismo
Archaea/química
Archaea/metabolismo
Bactérias/química
Bactérias/metabolismo
Ciclo do Carbono
Dióxido de Carbono/química
Dióxido de Carbono/metabolismo
Catálise
Ciclo do Ácido Cítrico
Ferredoxinas/metabolismo
Concentração de Íons de Hidrogênio
Fontes Hidrotermais
Ferro/metabolismo
Proteínas com Ferro-Enxofre/metabolismo
Ácidos Cetoglutáricos/química
Ácidos Cetoglutáricos/metabolismo
Ácido Oxaloacético/química
Ácido Oxaloacético/metabolismo
Prótons
Ácido Pirúvico/química
Ácido Pirúvico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ferredoxins); 0 (Iron-Sulfur Proteins); 0 (Ketoglutaric Acids); 0 (Protons); 142M471B3J (Carbon Dioxide); 2F399MM81J (Oxaloacetic Acid); 72-89-9 (Acetyl Coenzyme A); 8558G7RUTR (Pyruvic Acid); 8ID597Z82X (alpha-ketoglutaric acid); E1UOL152H7 (Iron)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1002/iub.1632


  5 / 5778 MEDLINE  
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[PMID]:29284039
[Au] Autor:Cassim S; Raymond VA; Lapierre P; Bilodeau M
[Ad] Endereço:Laboratoire d'hépatologie cellulaire, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
[Ti] Título:From in vivo to in vitro: Major metabolic alterations take place in hepatocytes during and following isolation.
[So] Source:PLoS One;12(12):e0190366, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The liver plays a key role in maintaining physiological homeostasis and hepatocytes are largely responsible for this. The use of isolated primary hepatocytes has become an essential tool for the study of nutrient physiology, xenobiotic metabolism and several liver pathologies. Since hepatocytes are removed from their normal environment, the isolation procedure and in vitro culture of primary hepatocytes is partially known to induce undesired metabolic changes. We aimed to perform a thorough metabolic profiling of primary cells before, during and after isolation using state-of-the-art techniques. Extensive metabolite measurements using HPLC were performed in situ in the liver, during hepatocyte isolation using the two-step collagenase perfusion method and during in vitro cell culture for up to 48 hours. Assessment of mitochondrial respiratory capacity and ATP-linked respiration of isolated primary hepatocytes was performed using extracellular flux analysis. Primary hepatocytes displayed a drastic decrease in antioxidative-related metabolites (NADPH, NADP, GSH and GSSG) during the isolation procedure when compared to the in situ liver (P<0.001). Parallel assessment of citric acid cycle activity showed a significant decrease of up to 95% in Acetyl-CoA, Isocitrate/Citrate ratio, Succinate, Fumarate and Malate in comparison to the in situ liver (P<0.001). While the levels of several cellular energetic metabolites such as Adenosine, AMP, ADP and ATP were found to be progressively reduced during the isolation procedure and cell culture (P<0.001), higher ATP/ADP ratio and energy charge level were observed when primary cells were cultured in vitro compared to the in situ liver (P<0.05). In addition, a significant decrease in the respiratory capacity occurred after 24 hours in culture. Interestingly, this was not associated with a significant modification of ATP-linked respiration. In conclusion, major metabolic alterations occur immediately after hepatocytes are removed from the liver. These changes persist or increase during in vitro culture. These observations need to be taken into account when using primary hepatocytes for the study of metabolism or liver physiopathology.
[Mh] Termos MeSH primário: Hepatócitos/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Cromatografia Líquida de Alta Pressão
Ciclo do Ácido Cítrico
Técnicas In Vitro
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Mitocôndrias Hepáticas/metabolismo
Estresse Oxidativo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antioxidants)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171229
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190366


  6 / 5778 MEDLINE  
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[PMID]:29225125
[Au] Autor:Shimada N; Takasawa R; Tanuma SI
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
[Ti] Título:Interdependence of GLO I and PKM2 in the Metabolic shift to escape apoptosis in GLO I-dependent cancer cells.
[So] Source:Arch Biochem Biophys;638:1-7, 2018 01 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many cancer cells undergo metabolic reprogramming known as the Warburg effect, which is characterized by a greater dependence on glycolysis for ATP generation, even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis and which is known to be highly expressed in many cancer cells. Thus, specific inhibitors of GLO I are expected to be effective anticancer drugs. We previously discovered a novel GLO I inhibitor named TLSC702. Although the strong inhibitory activity of TLSC702 was observed in the in vitro enzyme assay, higher concentrations were required to induce apoptosis at the cellular level. One of the proposed reasons for this difference is that cancer cells alter the energy metabolism leading them to become more dependent on mitochondrial respiration than glycolysis (Metabolic shift) to avoid apoptosis induction. Thus, we assumed that combination of TLSC702 with shikonin-a specific inhibitor of pyruvate kinase M2 (PKM2) that acts as a driver of TCA cycle by supplying pyruvate and which is known to be specifically expressed in cancer cells-would have anticancer effects. We herein show the anticancer effects of combination treatment with TLSC702 and shikonin, and a possible anticancer mechanism.
[Mh] Termos MeSH primário: Apoptose
Proteínas de Transporte/metabolismo
Lactoilglutationa Liase/metabolismo
Proteínas de Membrana/metabolismo
Proteínas de Neoplasias/metabolismo
Neoplasias/enzimologia
Piruvato Quinase/metabolismo
Hormônios Tireóideos/metabolismo
[Mh] Termos MeSH secundário: Butiratos/farmacologia
Proteínas de Transporte/antagonistas & inibidores
Proteínas de Transporte/genética
Linhagem Celular Tumoral
Ciclo do Ácido Cítrico/efeitos dos fármacos
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Lactoilglutationa Liase/antagonistas & inibidores
Lactoilglutationa Liase/genética
Proteínas de Membrana/antagonistas & inibidores
Proteínas de Membrana/genética
Naftoquinonas/farmacologia
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Neoplasias/tratamento farmacológico
Neoplasias/genética
Neoplasias/patologia
Piruvato Quinase/antagonistas & inibidores
Piruvato Quinase/genética
Ácido Pirúvico/metabolismo
Tiazóis/farmacologia
Hormônios Tireóideos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3-(1,3-benzothiazol-2-yl)-4-(4-methoxyphenyl)but-3-enoic acid); 0 (Butyrates); 0 (Carrier Proteins); 0 (Membrane Proteins); 0 (Naphthoquinones); 0 (Neoplasm Proteins); 0 (Thiazoles); 0 (Thyroid Hormones); 0 (thyroid hormone-binding proteins); 3IK6592UBW (shikonin); 8558G7RUTR (Pyruvic Acid); EC 2.7.1.40 (Pyruvate Kinase); EC 4.4.1.5 (GLO1 protein, human); EC 4.4.1.5 (Lactoylglutathione Lyase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE


  7 / 5778 MEDLINE  
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[PMID]:27776981
[Au] Autor:Kelly RS; Dahlin A; McGeachie MJ; Qiu W; Sordillo J; Wan ES; Wu AC; Lasky-Su J
[Ad] Endereço:Channing Division of Network Medicine, Brigham Women's Hospital and Harvard Medical School, Boston, MA.
[Ti] Título:Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic.
[So] Source:Chest;151(2):262-277, 2017 Feb.
[Is] ISSN:1931-3543
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age. In particular, acetate, adenosine, alanine, hippurate, succinate, threonine, and trans-aconitate, and pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were all identified as significant in at least two studies. There were also a number of nonreplicated results; however, the literature is not yet sufficiently developed to determine whether these represent spurious findings or reflect the substantial heterogeneity and limited statistical power in the studies and their methods to date. This review highlights the need for additional asthma metabolomic studies to explore these issues, and, further, the need for standardized methods in the way these studies are conducted. We conclude by discussing the potential of translation of these metabolomic findings into clinically useful biomarkers and the crucial role that integrated omics is likely to play in this endeavor.
[Mh] Termos MeSH primário: Asma/metabolismo
Biomarcadores/metabolismo
Hipóxia/metabolismo
Inflamação/metabolismo
Metabolômica
[Mh] Termos MeSH secundário: Testes Respiratórios
Ciclo do Ácido Cítrico
Seres Humanos
Metabolismo dos Lipídeos
Estresse Oxidativo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  8 / 5778 MEDLINE  
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[PMID]:29281667
[Au] Autor:Wang Y; Deng GG; Davies KP
[Ad] Endereço:Department of Urology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
[Ti] Título:Urothelial MaxiK-activity regulates mucosal and detrusor metabolism.
[So] Source:PLoS One;12(12):e0189387, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is increasing evidence for a role of MaxiK potassium channel-activity in regulating the metabolism and intracellular signaling of non-contractile bladder mucosal tissues. At present however no studies have determined the impact of urothelial MaxiK-activity on overall bladder metabolism. To address this we have investigated the effect of bladder lumen instillation of the MaxiK inhibitor, iberiotoxin (IBTX), on mucosal and detrusor metabolism using metabolomics. Since IBTX does not cross plasma membranes, when instilled into the bladder lumen it would only effect urothelially expressed MaxiK-activity. Surprisingly IBTX treatment caused more effect on the metabolome of the detrusor than mucosa (the levels of 17% of detected detrusor metabolites were changed in comparison to 6% of metabolites in mucosal tissue following IBTX treatment). In mucosal tissues, the major effects can be linked to mitochondrial-associated metabolism whereas in detrusor there were additional changes in energy generating pathways (such as glycolysis and the TCA cycle). In the detrusor, changes in metabolism are potentially a result of IBTX effecting MaxiK-linked signaling pathways between the mucosa and detrusor, secondary to changes in physiological activity or a combination of both. Overall we demonstrate that urothelial MaxiK-activity plays a significant role in determining mitochondrially-associated metabolism in mucosal tissues, which effects the metabolism of detrusor tissue. Our work adds further evidence that the urothelium plays a major role in determining overall bladder physiology. Since decreased MaxiK-activity is associated with several bladder pathophysiology's, the changes in mucosal metabolism reported here may represent novel downstream targets for therapeutic interventions.
[Mh] Termos MeSH primário: Bexiga Urinária/metabolismo
Urotélio/metabolismo
[Mh] Termos MeSH secundário: Animais
Ciclo do Ácido Cítrico
Histidina/metabolismo
Metabolômica
Mitocôndrias/metabolismo
Ratos
Ratos Endogâmicos F344
Sulfonas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Sulfones); 4QD397987E (Histidine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189387


  9 / 5778 MEDLINE  
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[PMID]:29216582
[Au] Autor:Fiori J; Amadesi E; Fanelli F; Tropeano CV; Rugolo M; Gotti R
[Ad] Endereço:Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy. Electronic address: jessica.fiori@unibo.it.
[Ti] Título:Cellular and mitochondrial determination of low molecular mass organic acids by LC-MS/MS.
[So] Source:J Pharm Biomed Anal;150:33-38, 2018 Feb 20.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A selective and sensitive method for the determination of low molecular mass organic acids (LMMOAs) in cell and mitochondrial extracts is presented. The analytical method consists in the separation by reversed phase liquid chromatography and detection with tandem mass spectrometry (LC-MS/MS) of the LMMOAs like malic, succinic, formic and citric acids. These acids are among the cellular intermediates of the tricarboxylic acid cycle (TCA), thus their quantitation can provide essential information about the catabolic and anabolic processes occurring in cells under physiological and pathological conditions. The analytical method was fully validated in terms of linearity, detection and quantification limits, recovery and precision. Detection limits (LOD) for malic, succinic and fumaric acids were in the range of 1-10nM, while 20nM was obtained for citric acid. Analytical recovery in cell and mitochondrial extracts was found between 88 and 105% (CV% ≤7.1) and matrix effect was estimated to be less than 108%. The LC-MS/MS method applied to the quantification of TCA cycle metabolites revealed a different distribution of the four acids in cells and mitochondria, and it could be used to monitoring metabolic alterations associated with TCA cycle and oxidative phosphorylation dysfunctions.
[Mh] Termos MeSH primário: Ácidos Acíclicos/análise
Cromatografia de Fase Reversa/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Ácidos Acíclicos/metabolismo
Ciclo do Ácido Cítrico
Seres Humanos
Limite de Detecção
Mitocôndrias/metabolismo
Peso Molecular
Compostos Orgânicos/análise
Compostos Orgânicos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Acids, Acyclic); 0 (Organic Chemicals)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


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[PMID]:29244852
[Au] Autor:Ott E; Kawaguchi Y; Kölbl D; Chaturvedi P; Nakagawa K; Yamagishi A; Weckwerth W; Milojevic T
[Ad] Endereço:Department of Biophysical Chemistry, University of Vienna, Vienna, Austria.
[Ti] Título:Proteometabolomic response of Deinococcus radiodurans exposed to UVC and vacuum conditions: Initial studies prior to the Tanpopo space mission.
[So] Source:PLoS One;12(12):e0189381, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The multiple extremes resistant bacterium Deinococcus radiodurans is able to withstand harsh conditions of simulated outer space environment. The Tanpopo orbital mission performs a long-term space exposure of D. radiodurans aiming to investigate the possibility of interplanetary transfer of life. The revealing of molecular machinery responsible for survivability of D. radiodurans in the outer space environment can improve our understanding of underlying stress response mechanisms. In this paper, we have evaluated the molecular response of D. radiodurans after the exposure to space-related conditions of UVC irradiation and vacuum. Notably, scanning electron microscopy investigations showed that neither morphology nor cellular integrity of irradiated cells was affected, while integrated proteomic and metabolomic analysis revealed numerous molecular alterations in metabolic and stress response pathways. Several molecular key mechanisms of D. radiodurans, including the tricarboxylic acid cycle, the DNA damage response systems, ROS scavenging systems and transcriptional regulators responded in order to cope with the stressful situation caused by UVC irradiation under vacuum conditions. These results reveal the effectiveness of the integrative proteometabolomic approach as a tool in molecular analysis of microbial stress response caused by space-related factors.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Deinococcus/efeitos da radiação
Proteoma/metabolismo
[Mh] Termos MeSH secundário: Ciclo do Ácido Cítrico
Deinococcus/metabolismo
Deinococcus/ultraestrutura
Viabilidade Microbiana
Voo Espacial
Raios Ultravioleta
Vácuo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Proteome)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189381



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