Base de dados : MEDLINE
Pesquisa : D08.811.277.040.025.325.750 [Categoria DeCS]
Referências encontradas : 1471 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 148 ir para página                         

  1 / 1471 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29254313
[Au] Autor:Goren A; Naccarato T; Situm M; Kovacevic M; Lotti T; McCoy J
[Ad] Endereço:Applied Biology, Inc., Irvine, CA, USA.
[Ti] Título:Mechanism of action of minoxidil in the treatment of androgenetic alopecia is likely mediated by mitochondrial adenosine triphosphate synthase-induced stem cell differentiation.
[So] Source:J Biol Regul Homeost Agents;31(4):1049-1053, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia.
[Mh] Termos MeSH primário: Alopecia/tratamento farmacológico
Folículo Piloso/efeitos dos fármacos
Minoxidil/uso terapêutico
Mitocôndrias/efeitos dos fármacos
ATPases Mitocondriais Próton-Translocadoras/genética
Células-Tronco/efeitos dos fármacos
Vasodilatadores/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Alopecia/enzimologia
Alopecia/genética
Alopecia/patologia
Cálcio/metabolismo
Diferenciação Celular/efeitos dos fármacos
Expressão Gênica
Folículo Piloso/enzimologia
Folículo Piloso/patologia
Seres Humanos
Transporte de Íons/efeitos dos fármacos
Masculino
Meia-Idade
Mitocôndrias/enzimologia
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Células-Tronco/enzimologia
Células-Tronco/patologia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vasodilator Agents); 5965120SH1 (Minoxidil); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


  2 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29177973
[Au] Autor:Niu Y; Moghimyfiroozabad S; Safaie S; Yang Y; Jonas EA; Alavian KN
[Ad] Endereço:Division of Brain Sciences, Department of Medicine, Imperial College London, E508, Burlington Danes Hammersmith Hospital, DuCane Road, London, W12 0NN, UK.
[Ti] Título:Phylogenetic Profiling of Mitochondrial Proteins and Integration Analysis of Bacterial Transcription Units Suggest Evolution of F1Fo ATP Synthase from Multiple Modules.
[So] Source:J Mol Evol;85(5-6):219-233, 2017 Dec.
[Is] ISSN:1432-1432
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:ATP synthase is a complex universal enzyme responsible for ATP synthesis across all kingdoms of life. The F-type ATP synthase has been suggested to have evolved from two functionally independent, catalytic (F1) and membrane bound (Fo), ancestral modules. While the modular evolution of the synthase is supported by studies indicating independent assembly of the two subunits, the presence of intermediate assembly products suggests a more complex evolutionary process. We analyzed the phylogenetic profiles of the human mitochondrial proteins and bacterial transcription units to gain additional insight into the evolution of the F-type ATP synthase complex. In this study, we report the presence of intermediary modules based on the phylogenetic profiles of the human mitochondrial proteins. The two main intermediary modules comprise the α ß hexamer in the F1 and the c-subunit ring in the Fo. A comprehensive analysis of bacterial transcription units of F1Fo ATP synthase revealed that while a long and constant order of F1Fo ATP synthase genes exists in a majority of bacterial genomes, highly conserved combinations of separate transcription units are present among certain bacterial classes and phyla. Based on our findings, we propose a model that includes the involvement of multiple modules in the evolution of F1Fo ATP synthase. The central and peripheral stalk subunits provide a link for the integration of the F1/Fo modules.
[Mh] Termos MeSH primário: ATPases Mitocondriais Próton-Translocadoras/genética
ATPases Mitocondriais Próton-Translocadoras/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/biossíntese
Evolução Molecular
Seres Humanos
Mitocôndrias/genética
Mitocôndrias/metabolismo
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Filogenia
Domínios Proteicos
Elementos Estruturais de Proteínas/genética
Transcrição Genética/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.- (F1F0-ATP synthase); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1007/s00239-017-9819-3


  3 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28748739
[Au] Autor:Ahamad MNU; Ali ME; Hossain MAM; Asing A; Sultana S; Jahurul MHA
[Ad] Endereço:a Nanotechnology and Catalysis Research Center, Institute of Graduate Studies , University of Malaya , Kuala Lumpur , Malaysia.
[Ti] Título:Multiplex PCR assay discriminates rabbit, rat and squirrel meat in food chain.
[So] Source:Food Addit Contam Part A Chem Anal Control Expo Risk Assess;34(12):2043-2057, 2017 Dec.
[Is] ISSN:1944-0057
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rabbit meat is receiving increasing attention because it contains a high level of proteins with relatively little fat. On the other hand, squirrel meat is served in upper-class meals in certain countries, so is sold at higher prices. The other side of the coin is rat meat, which has family ties with rabbit and squirrel but poses substantial threats to public health because it is a potential carrier of several zoonotic organisms. Recently, rat meat was mislabelled and sold as lamb after chemical modification. Thus, the chances of rabbit and squirrel meat substitution by rat meat cannot be ruled out. For the first time, a multiplex PCR assay was developed in Malaysia for the discriminatory identification of rat, rabbit and squirrel in the food chain. Rabbit (123 bp), rat (108 bp) and squirrel (243 bp) targets were amplified from ATP6 and cytb genes, along with a eukaryotic internal control (141bp). The products were sequenced and cross-tested against 22 species. A total of 81 reference samples and 72 meatball specimens were screened to validate the assay. Analyte stability was evaluated through boiling, autoclaving and micro-oven cooking. The tested lower limits of detection were 0.01 ng DNA for pure meat and 0.1% for meatballs.
[Mh] Termos MeSH primário: Contaminação de Alimentos/análise
Abastecimento de Alimentos
Carne/análise
Reação em Cadeia da Polimerase Multiplex
Coelhos/genética
Ratos/genética
Sciuridae/genética
[Mh] Termos MeSH secundário: Animais
Citocromos b/genética
Malásia
ATPases Mitocondriais Próton-Translocadoras/genética
ATPases Mitocondriais Próton-Translocadoras/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9035-37-4 (Cytochromes b); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[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:170728
[St] Status:MEDLINE
[do] DOI:10.1080/19440049.2017.1359752


  4 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29054413
[Au] Autor:Mordel P; Schaeffer S; Dupas Q; Laville MA; Gérard M; Chapon F; Allouche S
[Ad] Endereço:Normandie Univ, UNICAEN, CHU Caen, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14032, France.
[Ti] Título:A 2 bp deletion in the mitochondrial ATP 6 gene responsible for the NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome.
[So] Source:Biochem Biophys Res Commun;494(1-2):133-137, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial (mt) DNA-associated NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) syndrome is due to mutation in the MT-ATP6 gene. We report the case of a 18-year-old man who presented with deafness, a myoclonic epilepsy, muscle weakness since the age of 10 and further developed a retinitis pigmentosa and ataxia. The whole mtDNA analysis by next-generation sequencing revealed the presence of the 2 bp microdeletion m.9127-9128 del AT in the ATP6 gene at 82% heteroplasmy in muscle and to a lower load in blood (10-20%) and fibroblasts (50%). Using the patient's fibroblasts, we demonstrated a 60% reduction of the oligomycin-sensitive ATPase hydrolytic activity, a 40% decrease in the ATP synthesis and determination of the mitochondrial membrane potential using the fluorescent probe tetramethylrhodamine, ethyl ester indicated a significant reduction in oligomycin sensitivity. In conclusion, we demonstrated that this novel AT deletion in the ATP6 gene is pathogenic and responsible for the NARP syndrome.
[Mh] Termos MeSH primário: Miopatias Mitocondriais/enzimologia
Miopatias Mitocondriais/genética
ATPases Mitocondriais Próton-Translocadoras/genética
Retinite Pigmentosa/enzimologia
Retinite Pigmentosa/genética
Deleção de Sequência
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Adenosina Trifosfatases/metabolismo
Trifosfato de Adenosina/metabolismo
Sequência de Bases
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Células Cultivadas
Análise Mutacional de DNA
DNA Mitocondrial/genética
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Masculino
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Oligomicinas/farmacologia
Síndrome
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (DNA, Mitochondrial); 0 (Membrane Proteins); 0 (Oligomycins); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases); EC 3.6.3.14 (MT-ATP6 protein, human); EC 3.6.3.14 (oligomycin sensitivity-conferring protein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171022
[St] Status:MEDLINE


  5 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28882384
[Au] Autor:Nath S
[Ad] Endereço:Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India. Electronic address: sunath@dbeb.iitd.ac.in.
[Ti] Título:Two-ion theory of energy coupling in ATP synthesis rectifies a fundamental flaw in the governing equations of the chemiosmotic theory.
[So] Source:Biophys Chem;230:45-52, 2017 Nov.
[Is] ISSN:1873-4200
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The vital coupled processes of oxidative phosphorylation and photosynthetic phosphorylation synthesize molecules of adenosine-5'-triphosphate (ATP), the universal biological energy currency, and sustain all life on our planet. The chemiosmotic theory of energy coupling in oxidative and photophosphorylation was proposed by Mitchell >50years ago. It has had a contentious history, with part of the accumulated body of experimental evidence supporting it, and part of it in conflict with the theory. Although the theory was strongly criticized by many prominent scientists, the controversy has never been resolved. Here, the mathematical steps of Mitchell's original derivation leading to the principal equation of the chemiosmotic theory are scrutinized, and a fundamental flaw in them has been identified. Surprisingly, this flaw had not been detected earlier. Discovery of such a defect negates, or at least considerably weakens, the theoretical foundations on which the chemiosmotic theory is based. Ad hoc or simplistic ways to remedy this defect are shown to be scientifically unproductive and sterile. A novel two-ion theory of biological energy coupling salvages the situation by rectifying the fundamental flaw in the chemiosmotic theory, and the governing equations of the new theory have been shown to accurately quantify and predict extensive recent experimental data on ATP synthesis by F F -ATP synthase without using adjustable parameters. Some major biological implications arising from the new thinking are discussed. The principles of energy transduction and coupling proposed in the new paradigm are shown to be of a very general and universal nature. It is concluded that the timely availability after a 25-year research struggle of Nath's torsional mechanism of energy transduction and ATP synthesis is a rational alternative that has the power to solve the problems arising from the past, and also meet present and future challenges in this important interdisciplinary field of research.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/química
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Concentração de Íons de Hidrogênio
Íons/química
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Modelos Moleculares
Fosforilação Oxidativa
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ions); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.- (F1F0-ATP synthase); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE


  6 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28873407
[Au] Autor:Tulloch LB; Menzies SK; Fraser AL; Gould ER; King EF; Zacharova MK; Florence GJ; Smith TK
[Ad] Endereço:EaStChem School of Chemistry and School of Biology, Biomedical Science Research Complex, University of St Andrews, St Andrews, Fife, United Kingdom.
[Ti] Título:Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues.
[So] Source:PLoS Negl Trop Dis;11(9):e0005886, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1, a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation. We used compound 3, a diazirine- and alkyne-containing bi-functional photo-affinity probe analogue of our lead B-THP-T, compound 1, to identify potential targets of our lead compound in the procyclic form T. brucei. Bi-functional compound 3 was UV cross-linked to its target(s) in vivo and biotin affinity or Cy5.5 reporter tags were subsequently appended by Cu(II)-catalysed azide-alkyne cycloaddition. The biotinylated protein adducts were isolated with streptavidin affinity beads and subsequent LC-MSMS identified the FoF1-ATP synthase (mitochondrial complex V) as a potential target. This target identification was confirmed using various different approaches. We show that (i) compound 1 decreases cellular ATP levels (ii) by inhibiting oxidative phosphorylation (iii) at the FoF1-ATP synthase. Furthermore, the use of GFP-PTP-tagged subunits of the FoF1-ATP synthase, shows that our compounds bind specifically to both the α- and ß-subunits of the ATP synthase. The FoF1-ATP synthase is a target of our simplified acetogenin-type analogues. This mitochondrial complex is essential in both procyclic and bloodstream forms of T. brucei and its identification as our target will enable further inhibitor optimisation towards future drug discovery. Furthermore, the photo-affinity labeling technique described here can be readily applied to other drugs of unknown targets to identify their modes of action and facilitate more broadly therapeutic drug design in any pathogen or disease model.
[Mh] Termos MeSH primário: Produtos Biológicos/farmacologia
Descoberta de Drogas/métodos
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Sondas Moleculares
Marcadores de Fotoafinidade
Tripanossomicidas/farmacologia
Trypanosoma brucei brucei/efeitos dos fármacos
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Produtos Biológicos/análise
Produtos Biológicos/química
Produtos Biológicos/metabolismo
Desenho de Drogas
Seres Humanos
ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores
Fosforilação Oxidativa
Proteínas de Protozoários/química
Proteínas de Protozoários/metabolismo
Coloração e Rotulagem/métodos
Tripanossomicidas/análise
Tripanossomicidas/química
Tripanossomicidas/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biological Products); 0 (Molecular Probes); 0 (Photoaffinity Labels); 0 (Protozoan Proteins); 0 (Trypanocidal Agents); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005886


  7 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28859158
[Au] Autor:Kanaporis G; Treinys R; Fischmeister R; Jurevicius J
[Ad] Endereço:Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
[Ti] Título:Metabolic inhibition reduces cardiac L-type Ca2+ channel current due to acidification caused by ATP hydrolysis.
[So] Source:PLoS One;12(8):e0184246, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolic stress evoked by myocardial ischemia leads to impairment of cardiac excitation and contractility. We studied the mechanisms by which metabolic inhibition affects the activity of L-type Ca2+ channels (LTCCs) in frog ventricular myocytes. Metabolic inhibition induced by the protonophore FCCP (as well as by 2,4- dinitrophenol, sodium azide or antimycin A) resulted in a dose-dependent reduction of LTCC current (ICa,L) which was more pronounced during ß-adrenergic stimulation with isoprenaline. ICa,L was still reduced by metabolic inhibition even in the presence of 3 mM intracellular ATP, or when the cell was dialysed with cAMP or ATP-γ-S to induce irreversible thiophosphorylation of LTCCs, indicating that reduction in ICa,L is not due to ATP depletion and/or reduced phosphorylation of the channels. However, the effect of metabolic inhibition on ICa,L was strongly attenuated when the mitochondrial F1F0-ATP-synthase was blocked by oligomycin or when the cells were dialysed with the non-hydrolysable ATP analogue AMP-PCP. Moreover, increasing the intracellular pH buffering capacity or intracellular dialysis of the myocytes with an alkaline solution strongly attenuated the inhibitory effect of FCCP on ICa,L. Thus, our data demonstrate that metabolic inhibition leads to excessive ATP hydrolysis by the mitochondrial F1F0-ATP-synthase operating in the reverse mode and this results in intracellular acidosis causing the suppression of ICa,L. Limiting ATP break-down by F1F0-ATP-synthase and the consecutive development of intracellular acidosis might thus represent a potential therapeutic approach for maintaining a normal cardiac function during ischemia.
[Mh] Termos MeSH primário: Canais de Cálcio Tipo L/metabolismo
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Contração Miocárdica/genética
Isquemia Miocárdica/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Canais de Cálcio Tipo L/genética
Carbonil Cianeto p-Trifluormetoxifenil Hidrazona/administração & dosagem
Ventrículos do Coração/metabolismo
Ventrículos do Coração/fisiopatologia
Isoproterenol/administração & dosagem
Mitocôndrias/enzimologia
Células Musculares/efeitos dos fármacos
Células Musculares/metabolismo
Contração Miocárdica/efeitos dos fármacos
Isquemia Miocárdica/genética
Isquemia Miocárdica/fisiopatologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/metabolismo
Miócitos Cardíacos/patologia
Rana esculenta
Estresse Fisiológico/efeitos dos fármacos
Estresse Fisiológico/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, L-Type); 370-86-5 (Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.- (F1F0-ATP synthase); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases); L628TT009W (Isoproterenol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184246


  8 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28850625
[Au] Autor:Lai N; Kummitha C; Hoppel C
[Ad] Endereço:Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, Virginia, United States of America.
[Ti] Título:Defects in skeletal muscle subsarcolemmal mitochondria in a non-obese model of type 2 diabetes mellitus.
[So] Source:PLoS One;12(8):e0183978, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Skeletal muscle resistance to insulin is related to accumulation of lipid-derived products, but it is not clear whether this accumulation is caused by skeletal muscle mitochondrial dysfunction. Diabetes and obesity are reported to have a selective effect on the function of subsarcolemmal and interfibrillar mitochondria in insulin-resistant skeletal muscle. The current study investigated the role of the subpopulations of mitochondria in the pathogenesis of insulin resistance in the absence of obesity. A non-obese spontaneous rat model of type 2 diabetes mellitus, (Goto-Kakizaki), was used to evaluate function and biochemical properties in both populations of skeletal muscle mitochondria. In subsarcolemmal mitochondria, minor defects are observed whereas in interfibrillar mitochondria function is preserved. Subsarcolemmal mitochondria defects characterized by a mild decline of oxidative phosphorylation efficiency are related to ATP synthase and structural alterations of inner mitochondria membrane but are considered unimportant because of the absence of defects upstream as shown with polarographic and spectrophometric assays. Fatty acid transport and oxidation is preserved in both population of mitochondria, whereas palmitoyl-CoA increased 25% in interfibrillar mitochondria of diabetic rats. Contrary to popular belief, these data provide compelling evidence that mitochondrial function is unaffected in insulin-resistant skeletal muscle from T2DM non-obese rats.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/metabolismo
Mitocôndrias Musculares/metabolismo
Músculo Esquelético/metabolismo
Sarcolema/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Masculino
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Fosforilação Oxidativa
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183978


  9 / 1471 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28841379
[Au] Autor:Nazari M; Serrill JD; Wan X; Nguyen MH; Anklin C; Gallegos DA; Smith AB; Ishmael JE; McPhail KL
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331, United States.
[Ti] Título:New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors.
[So] Source:J Med Chem;60(18):7850-7862, 2017 Sep 28.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mandelalides A-D (1-4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E-L (5-12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells. Macrolides 1 and 2 inhibit mitochondrial function similar to oligomycin A and apoptolidin A, selective inhibitors of the mammalian ATP synthase (complex V). 1 inhibits ATP synthase activity from isolated mitochondria and triggers caspase-dependent apoptosis in HeLa cells, which are more sensitive to inhibition by 1 in the presence of the glycolysis inhibitor 2-deoxyglucose. Thus, mandelalide cytotoxicity depends on basal metabolic phenotype; cells with an oxidative phenotype are most likely to be inhibited by the mandelalides.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Macrolídeos/química
Macrolídeos/farmacologia
Mitocôndrias/efeitos dos fármacos
ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Glicosilação
Células HEK293
Células HeLa
Seres Humanos
Mitocôndrias/enzimologia
Mitocôndrias/metabolismo
ATPases Mitocondriais Próton-Translocadoras/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Macrolides); 0 (mandelalide A); 0 (mandelalide E); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00990


  10 / 1471 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28781258
[Au] Autor:Medvedev DV; Zvyagina VI; Uryasev OM; Belskikh ES; Bulatetskiy SV; Ryabkov AN
[Ad] Endereço:Ryazan State Medical University.
[Ti] Título:[Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia].
[Ti] Título:Metabolicheskie izmeneniia v mitokhondriiakh legkikh pri éksperimental'noi gipergomotsisteinemii u krys..
[So] Source:Biomed Khim;63(3):248-254, 2017 May.
[Is] ISSN:2310-6972
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Hyperhomocysteinemia is a risk factor for many human diseases, including pulmonary pathologies. In this context much interest attracts secondary mitochondrial dysfunction, which is an important link in pathogenesis of diseases associated with hyperhomocysteinemia. The study was conducted using male Wistar rats. It was found that under conditions of severe hyperhomocysteinemia caused by administration of methionine, homocysteine was accumulated in lung mitochondria thus suggesting a direct toxic effect on these organelles. However, we have not observed any significant changes in the activity of mitochondrial enzymes involved in tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) and of cytoplasmic lactate dehydrogenase. Also there was no accumulation of lactic acid in the cytoplasm. Animals with severe hyperhomocysteinemia had higher levels of lung mitochondrial protein carbonylation, decreased reserve-adaptive capacity, and increased superoxide dismutase activity. These results indicate that severe hyperhomocysteinemia causes development of oxidative stress in lung mitochondria, which is compensated by activation of antioxidant protection. These changes were accompanied by a decrease in the concentration of mitochondrial nitric oxide metabolites. Introduction to animals a nonselective NO-synthase inhibitor L-NAME caused similar enhancement of mitochondrial protein carbonylation. It demonstrates importance of reducing bioavailability of nitric oxide, which is an antioxidant in physiological concentrations, in the development of oxidative stress in lung mitochondria during hyperhomocysteinemia. Key words: hyperhomocysteinemia, nitric oxide, lung, oxidative stress, mitochondria.
[Mh] Termos MeSH primário: Homocisteína/metabolismo
Hiper-Homocisteinemia/metabolismo
Pulmão/metabolismo
Metionina/efeitos adversos
Mitocôndrias/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Inibidores Enzimáticos/farmacologia
Homocisteína/agonistas
Seres Humanos
Hiper-Homocisteinemia/induzido quimicamente
Hiper-Homocisteinemia/patologia
L-Lactato Desidrogenase/metabolismo
Pulmão/efeitos dos fármacos
Pulmão/patologia
Masculino
Metionina/administração & dosagem
Mitocôndrias/metabolismo
ATPases Mitocondriais Próton-Translocadoras/metabolismo
NG-Nitroarginina Metil Éster/farmacologia
Óxido Nítrico/metabolismo
Fosforilação Oxidativa
Estresse Oxidativo/efeitos dos fármacos
Carbonilação Proteica/efeitos dos fármacos
Ratos
Ratos Wistar
Succinato Desidrogenase/metabolismo
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0LVT1QZ0BA (Homocysteine); 31C4KY9ESH (Nitric Oxide); AE28F7PNPL (Methionine); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 1.15.1.1 (Superoxide Dismutase); EC 1.3.99.1 (Succinate Dehydrogenase); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases); V55S2QJN2X (NG-Nitroarginine Methyl Ester)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE
[do] DOI:10.18097/PBMC20176303248



página 1 de 148 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde