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[PMID]:29323106
[Au] Autor:Samanta K; Mirams GR; Parekh AB
[Ad] Endereço:Department of Physiology, Anatomy and Genetics, Oxford University, Parks Road, Oxford, OX1 3PT, UK.
[Ti] Título:Sequential forward and reverse transport of the Na Ca exchanger generates Ca oscillations within mitochondria.
[So] Source:Nat Commun;9(1):156, 2018 01 11.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mitochondrial Ca homoeostasis regulates aerobic metabolism and cell survival. Ca flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca export is often through an electrogenic Na -Ca exchanger. Here, we report remarkable functional versatility in mitochondrial Na -Ca exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na -Ca exchange initially operates in reverse mode, transporting cytosolic Ca into the matrix. As matrix Ca rises, the exchanger reverts to its forward mode state, extruding Ca . Transitions between reverse and forward modes generate repetitive oscillations in matrix Ca . We further show that reverse mode Na -Ca activity is regulated by the mitochondrial fusion protein mitofusin 2. Our results demonstrate that reversible switching between transport modes of an ion exchanger molecule generates functionally relevant oscillations in the levels of the universal Ca messenger within an organelle.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Mitocôndrias/metabolismo
Trocador de Sódio e Cálcio/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico Ativo/fisiologia
Linhagem Celular
Seres Humanos
Potencial da Membrana Mitocondrial
Modelos Biológicos
Permeabilidade
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Sodium-Calcium Exchanger); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02638-2


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[PMID]:28448473
[Au] Autor:Pérez-Riesgo E; Gutiérrez LG; Ubierna D; Acedo A; Moyer MP; Núñez L; Villalobos C
[Ad] Endereço:Institute of Molecular Biology and Genetics (IBGM), National Research Council (CSIC), 47003 Valladolid, Spain. epercamh@gmail.com.
[Ti] Título:Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 27.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca remodeling includes critical changes in store-operated Ca entry (SOCE) and Ca store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca transport, a comprehensive view of Ca remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca transport in CRC. To this end, mRNA from normal human colonic NCM460 cells and human colon cancer HT29 cells was isolated and used as a template for transcriptomic sequencing and expression analysis using Ion Torrent technology. After data transformation and filtering, exploratory analysis revealed that both cell types were well segregated. In addition, differential gene expression using R and bioconductor packages show significant differences in expression of selected voltage-operated Ca channels and store-operated Ca entry players, transient receptor potential (TRP) channels, Ca release channels, Ca pumps, Na⁺/Ca exchanger isoforms and genes involved in mitochondrial Ca transport. These data provide the first comprehensive transcriptomic analysis of Ca remodeling in CRC.
[Mh] Termos MeSH primário: Canais de Cálcio/genética
Cálcio/metabolismo
Perfilação da Expressão Gênica
[Mh] Termos MeSH secundário: Canais de Cálcio/metabolismo
Linhagem Celular Tumoral
Análise por Conglomerados
Neoplasias Colorretais/genética
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Regulação da Expressão Gênica
Células HT29
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Análise de Componente Principal
Análise de Sequência de RNA
Trocador de Sódio e Cálcio/genética
Trocador de Sódio e Cálcio/metabolismo
Canais de Receptores Transientes de Potencial/genética
Canais de Receptores Transientes de Potencial/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (Sodium-Calcium Exchanger); 0 (Transient Receptor Potential Channels); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


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[PMID]:28692664
[Au] Autor:Williams RM; Winkfein RJ; Ginger RS; Green MR; Schnetkamp PP; Wheeler GN
[Ad] Endereço:School of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
[Ti] Título:A functional approach to understanding the role of NCKX5 in Xenopus pigmentation.
[So] Source:PLoS One;12(7):e0180465, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NCKX5 is an ion exchanger expressed mostly in pigment cells; however, the functional role for this protein in melanogenesis is not clear. A variant allele of SLC24A5, the gene encoding NCKX5, has been shown to correlate with lighter skin pigmentation in humans, indicating a key role for SLC24A5 in determining human skin colour. SLC24A5 expression has been found to be elevated in melanoma. Knockdown analyses have shown SLC24A5 to be important for pigmentation, but to date the function of this ion exchanger in melanogenesis has not been fully established. Our data suggest NCKX5 may have an alternative activity that is key to its role in the regulation of pigmentation. Here Xenopus laevis is employed as an in vivo model system to further investigate the function of NCKX5 in pigmentation. SLC24A5 is expressed in the melanophores as they differentiate from the neural crest and develop in the RPE of the eye. Morpholino knockdown and rescue experiments were designed to elucidate key residues and regions of the NCKX5 protein. Unilateral morpholino injection at the 2 cell stage resulted in a reduction of pigmentation in the eye and epidermis of one lateral side of the tadpole. Xenopus and human SLC24A5 can rescue the morpholino effects. Further rescue experiments including the use of ion exchange inactive SLC24A5 constructs raise the possibility that full ion exchanger function of NCKX5 may not be required for rescue of pigmentation.
[Mh] Termos MeSH primário: Pigmentação da Pele/genética
Trocador de Sódio e Cálcio/genética
Proteínas de Xenopus/genética
Xenopus laevis/genética
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Morfolinos/farmacologia
Mutação/genética
Fenótipo
Pigmentação da Pele/efeitos dos fármacos
Trocador de Sódio e Cálcio/metabolismo
Proteínas de Xenopus/metabolismo
Xenopus laevis/embriologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Morpholinos); 0 (Sodium-Calcium Exchanger); 0 (Xenopus Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180465


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[PMID]:28683437
[Au] Autor:Pelzl L; Hosseinzadeh Z; Al-Maghout T; Singh Y; Sahu I; Bissinger R; Schmidt S; Alkahtani S; Stournaras C; Toulany M; Lang F
[Ad] Endereço:Department of Internal Medicine III, Tuebingen, Germany.
[Ti] Título:Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells.
[So] Source:Cell Physiol Biochem;42(3):1240-1251, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. METHODS: In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (Δ[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. RESULTS: The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. CONCLUSIONS: Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells.
[Mh] Termos MeSH primário: Neoplasias Cerebelares/tratamento farmacológico
Resistência a Medicamentos Antineoplásicos
Regulação Neoplásica da Expressão Gênica
Meduloblastoma/tratamento farmacológico
Trocador de Sódio e Cálcio/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Cálcio/metabolismo
Linhagem Celular Tumoral
Neoplasias Cerebelares/genética
Cerebelo/efeitos dos fármacos
Cerebelo/metabolismo
Seres Humanos
Meduloblastoma/genética
Técnicas de Patch-Clamp
Isoformas de Proteínas/metabolismo
Sódio/metabolismo
Trocador de Sódio e Cálcio/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Isoforms); 0 (Sodium-Calcium Exchanger); 9NEZ333N27 (Sodium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1159/000478953


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[PMID]:28683095
[Au] Autor:Maltsev AV; Parsons SP; Kim MS; Tsutsui K; Stern MD; Lakatta EG; Maltsev VA; Monfredi O
[Ad] Endereço:Laboratory of Cardiovascular Science, NIA/NIH, Baltimore, Maryland, United States of America.
[Ti] Título:Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells.
[So] Source:PLoS One;12(7):e0179419, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Local Ca2+ Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. In the present study we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Our algorithm tracks points along the midline of the contracting cell. It uses these points as a coordinate system for affine transform, producing a transformed image series where the cell does not contract. Action potential-induced Ca2+ transients and LCRs were thereafter isolated from recording noise by applying a series of spatial filters. The LCR birth and death events were detected by a differential (frame-to-frame) sensitivity algorithm applied to each pixel (cell location). An LCR was detected when its signal changes sufficiently quickly within a sufficiently large area. The LCR is considered to have died when its amplitude decays substantially, or when it merges into the rising whole cell Ca2+ transient. Ultimately, our algorithm provides major LCR parameters such as period, signal mass, duration, and propagation path area. As the LCRs propagate within live cells, the algorithm identifies splitting and merging behaviors, indicating the importance of locally propagating Ca2+-induced-Ca2+-release for the fate of LCRs and for generating a powerful ensemble Ca2+ signal. Thus, our new computer algorithms eliminate motion artifacts and detect 2D local spatiotemporal events from recording noise and global signals. While the algorithms were developed to detect LCRs in sinoatrial nodal cells, they have the potential to be used in other applications in biophysics and cell physiology, for example, to detect Ca2+ wavelets (abortive waves), sparks and embers in muscle cells and Ca2+ puffs and syntillas in neurons.
[Mh] Termos MeSH primário: Algoritmos
Sinalização do Cálcio/fisiologia
Cálcio/metabolismo
Miócitos Cardíacos/fisiologia
Nó Sinoatrial/fisiologia
Software
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Animais
Canais de Cálcio Tipo L/fisiologia
Cobaias
Frequência Cardíaca/fisiologia
Transporte de Íons/fisiologia
Miócitos Cardíacos/citologia
Coelhos
Canal de Liberação de Cálcio do Receptor de Rianodina/fisiologia
Retículo Sarcoplasmático/metabolismo
Nó Sinoatrial/citologia
Trocador de Sódio e Cálcio/fisiologia
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, L-Type); 0 (Ryanodine Receptor Calcium Release Channel); 0 (Sodium-Calcium Exchanger); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179419


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[PMID]:28646126
[Au] Autor:Khananshvili D
[Ad] Endereço:From the Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel dhanan@post.tau.ac.il.
[Ti] Título:How a helix imposes palmitoylation of a membrane protein: What one can learn from NCX.
[So] Source:J Biol Chem;292(25):10753-10754, 2017 Jun 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Palmitoylation is a critical post-translational modification that anchors proteins to, and regulates transport across, the lipid bilayer. Palmitoylation enzymes have been assumed to select their substrates based on a protein's primary sequence, but a consensus sequence has been slow to emerge. A study of the sodium/calcium exchanger now suggests that secondary structure may hold the key to understanding the determinants of this modification.
[Mh] Termos MeSH primário: Bicamadas Lipídicas/metabolismo
Lipoilação/fisiologia
Processamento de Proteína Pós-Traducional/fisiologia
Trocador de Sódio e Cálcio/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Domínios Proteicos
Estrutura Secundária de Proteína
Trocador de Sódio e Cálcio/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipid Bilayers); 0 (Sodium-Calcium Exchanger)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.H116.773945


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[PMID]:28638869
[Au] Autor:Zhang Y; Yu L; Jin W; Fan H; Li M; Zhou T; Wan H; Yang J
[Ad] Endereço:Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
[Ti] Título:REDUCING TOXICITY AND INCREASING EFFICIENCY: ACONITINE WITH LIQUIRITIN AND GLYCYRRHETINIC ACID REGULATE CALCIUM REGULATORY PROTEINS IN RAT MYOCARDIAL CELL.
[So] Source:Afr J Tradit Complement Altern Med;14(4):69-79, 2017.
[Is] ISSN:2505-0044
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Compatibility of and is known to treat heart diseases such as heart failure and cardiac arrhythmias. This work answers the question that whether the active components (Aconitine, Liquiritin and Glycyrrhetinic Acid) of and could result in regulating intracellular calcium homeostasis and calcium cycling, and thereby verifies the therapeutic material basis. MATERIALS AND METHODS: The myocardial cells were divided into twelve groups randomly as control group, Aconitine group, nine different dose groups that orthogonal combined with Aconitine, Liquiritin and Glycyrrhetinic Acid, and Verapamil group. The myocardial cellular survival rate and morphology were assessed. The expression of calcium regulation protein(RyR2, NCX1, DHPR-a1) in the myocardial cell by Western-blotting. RESULTS: The results exhibited that Aconitine (120 uM) significantly damaged on myocardial cell, decreased the survival rate and expression of Na /Ca exchangers (NCX1) and dihydropteridine reducta-α1 (DHPR-a1), and increased the expression of ryanodine receptor type2 (RyR2) obviously. The compatibility groups (Aconitine, Liquiritin and Glycyrrhetinic Acid) all could against the damage on the myocardial cell by Aconitine at different levels. CONCLUSION: Aconitine with Liquiritin and Glycyrrhetinic Acid may regulate the expression of calcium-regulated proteins to protect myocardial cells from damage.
[Mh] Termos MeSH primário: Aconitina/farmacologia
Aconitum/química
Cálcio/metabolismo
Medicamentos de Ervas Chinesas/farmacologia
Flavanonas/farmacologia
Glucosídeos/farmacologia
Ácido Glicirretínico/farmacologia
Glycyrrhiza/química
Miócitos Cardíacos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Miócitos Cardíacos/metabolismo
Ratos
Canal de Liberação de Cálcio do Receptor de Rianodina/genética
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
Trocador de Sódio e Cálcio/genética
Trocador de Sódio e Cálcio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 0 (Flavanones); 0 (Glucosides); 0 (RyR2 protein, rat); 0 (Ryanodine Receptor Calcium Release Channel); 0 (Sodium-Calcium Exchanger); 0 (sodium-calcium exchanger 1); P540XA09DR (Glycyrrhetinic Acid); SY7Q814VUP (Calcium); T0O79T74CD (liquiritin); X8YN71D5WC (Aconitine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.21010/ajtcam.v14i4.9


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[PMID]:28637456
[Au] Autor:Yu X; Zhao XD; Bao RQ; Yu JY; Zhang GX; Chen JW
[Ad] Endereço:Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou, 215123, People's Republic of China.
[Ti] Título:The modified Yi qi decoction protects cardiac ischemia-reperfusion induced injury in rats.
[So] Source:BMC Complement Altern Med;17(1):330, 2017 Jun 21.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To investigate the effects and involved mechanisms of the modified Yi Qi decoction (MYQ) in cardiac ischemia-reperfusion (IR) induced injury. METHODS: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion, low or high dose decoction of MYQ was administrated orally for 1 week or 1 month. RESULTS: Both in 1 week and 1 month IR rat groups, cardiac function indexes were significantly impaired compared with sham group rats, accompanied with higher ratio of infarct size to risk size, decreased expressions of sodium calcium exchanger (NCX1) and sarcoplasmic reticulum Ca -ATPase (Serca2a), and different expressions of autophagic proteins, Beclin-1 and LC3. Treatment with MYQ (low or high dose) for 1 week showed no marked beneficial effects on cardiac function and cardiac injury (ratio of infarct size to risk size), although expressions of anti-apoptotic protein, Bcl-2, NCX1 and Serca2a were increased. Treatment with MYQ (low or high dose) for 1 month showed significantly improved effects on cardiac function and cardiac injury (ratio of infarct size to risk size), accompanied with increase of Bcl-2, NCX1 and Serca2a expressions, and decrease of Bax (a pro-apoptotic protein) and Beclin-1 expressions. CONCLUSIONS: The results show that MYQ have potential therapeutic effects on IR-induced cardiac injury, which may be through regulation of apoptotic proteins, cytosolic Ca handling proteins and autophagic proteins signal pathways.
[Mh] Termos MeSH primário: Medicamentos de Ervas Chinesas/administração & dosagem
Traumatismo por Reperfusão Miocárdica/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Beclina-1/genética
Beclina-1/metabolismo
Seres Humanos
Masculino
Isquemia Miocárdica/cirurgia
Traumatismo por Reperfusão Miocárdica/genética
Traumatismo por Reperfusão Miocárdica/metabolismo
Traumatismo por Reperfusão Miocárdica/fisiopatologia
Qi
Ratos
Ratos Sprague-Dawley
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Trocador de Sódio e Cálcio/genética
Trocador de Sódio e Cálcio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Beclin-1); 0 (Drugs, Chinese Herbal); 0 (Sodium-Calcium Exchanger); 0 (sodium-calcium exchanger 1); EC 3.6.3.8 (Atp2a2 protein, rat); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-1829-6


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[PMID]:28573241
[Au] Autor:Li Z; Li S; Hu L; Li F; Cheung AC; Shao W; Que Y; Leung GP; Yang C
[Ad] Endereço:Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, P.R. China.
[Ti] Título:MECHANISMS UNDERLYING ACTION OF INJECTION, A TRADITIONAL CHINESE MEDICINE IN CARDIAC FUNCTION IMPROVEMENT.
[So] Source:Afr J Tradit Complement Altern Med;14(2):241-252, 2017.
[Is] ISSN:2505-0044
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: As a bioactive composite extracted from American cockroach, injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF. MATERIALS AND METHODS: The effects of XML on the cardiac function in isolated rat heart were measured. A Ca imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca channels. Meanwhile, the effects of XML on the activities of Na+/K+ ATPase and sodium/calcium exchanger were measured. In addition, the level of reactive oxygen species and the protein expressions for the superoxide dismutase and hemeoxygenase were determined in the cardiomyocytes. RESULTS: The results showed that XML increased the electrical impulse-induced [Ca ] in H9c2 cells, which was dependant on extracellular Ca and was abolished by ML218-HCl (a T-type Ca channels antagonist) but not nimodipine (a L-type Ca channels antagonist). Ouabain, a Na+/K+-ATPase inhibitor, increased the electrical impulse-induced [Ca ] , which was significantly inhibited by XML. Moreover, XML markedly inhibited the Na+/K+ ATPase activity in H9c2 cells. In addition, XML notably reduced the production of reactive oxygen species and enhanced the protein expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and hemeoxygenase 1 in H9c2 cell. CONCLUSION: Our findings pave the ways to the better understandings of the therapeutic effects of XML on cardiovascular system.
[Mh] Termos MeSH primário: Canais de Cálcio/metabolismo
Cálcio/metabolismo
Medicamentos de Ervas Chinesas/farmacologia
Coração/efeitos dos fármacos
Miócitos Cardíacos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Compostos Azabicíclicos/farmacologia
Benzamidas/farmacologia
Bloqueadores dos Canais de Cálcio/farmacologia
Cardiotônicos/farmacologia
Linhagem Celular
Baratas/química
Coração/fisiologia
Heme Oxigenase-1/metabolismo
Medicina Tradicional Chinesa
Miócitos Cardíacos/metabolismo
Nimodipino/farmacologia
Ouabaína/farmacologia
Ratos
Espécies Reativas de Oxigênio/metabolismo
Trocador de Sódio e Cálcio/metabolismo
ATPase Trocadora de Sódio-Potássio/metabolismo
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azabicyclo Compounds); 0 (Benzamides); 0 (Calcium Channel Blockers); 0 (Calcium Channels); 0 (Cardiotonic Agents); 0 (Drugs, Chinese Herbal); 0 (ML218 compound); 0 (Reactive Oxygen Species); 0 (Sodium-Calcium Exchanger); 0 (xinmailong); 57WA9QZ5WH (Nimodipine); 5ACL011P69 (Ouabain); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.15.1.1 (Superoxide Dismutase); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.21010/ajtcam.v14i2.26


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[PMID]:28572509
[Au] Autor:Giladi M; van Dijk L; Refaeli B; Almagor L; Hiller R; Man P; Forest E; Khananshvili D
[Ad] Endereço:From the Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel.
[Ti] Título:Dynamic distinctions in the Na /Ca exchanger adopting the inward- and outward-facing conformational states.
[So] Source:J Biol Chem;292(29):12311-12323, 2017 Jul 21.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Na /Ca exchanger (NCX) proteins operate through the alternating access mechanism, where the ion-binding pocket is exposed in succession either to the extracellular or the intracellular face of the membrane. The archaeal NCX_Mj ( NCX) system was used to resolve the backbone dynamics in the inward-facing (IF) and outward-facing (OF) states by analyzing purified preparations of apo- and ion-bound forms of NCX_Mj-WT and its mutant, NCX_Mj-5L6-8. First, the exposure of extracellular and cytosolic vestibules to the bulk phase was evaluated as the reactivity of single cysteine mutants to a fluorescent probe, verifying that NCX_Mj-WT and NCX_Mj-5L6-8 preferentially adopt the OF and IF states, respectively. Next, hydrogen-deuterium exchange-mass spectrometry (HDX-MS) was employed to analyze the backbone dynamics profiles in proteins, preferentially adopting the OF (WT) and IF (5L6-8) states either in the presence or absence of ions. Characteristic differences in the backbone dynamics were identified between apo NCX_Mj-WT and NCX_Mj-5L6-8, thereby underscoring specific conformational patterns owned by the OF and IF states. Saturating concentrations of Na or Ca specifically modify HDX patterns, revealing that the ion-bound/occluded states are much more stable (rigid) in the OF than in the IF state. Conformational differences observed in the ion-occluded OF and IF states can account for diversifying the ion-release dynamics and apparent affinity ( ) at opposite sides of the membrane, where specific structure-dynamic elements can effectively match the rates of bidirectional ion movements at physiological ion concentrations.
[Mh] Termos MeSH primário: Proteínas Arqueais/química
Cálcio/metabolismo
Membrana Celular/química
Methanocaldococcus/metabolismo
Modelos Moleculares
Trocador de Sódio e Cálcio/química
Sódio/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Apoproteínas/química
Apoproteínas/genética
Apoproteínas/metabolismo
Proteínas Arqueais/genética
Proteínas Arqueais/metabolismo
Sítios de Ligação
Biologia Computacional
Cisteína/química
Medição da Troca de Deutério
Cinética
Ligantes
Mutagênese Insercional
Mutação
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Estabilidade Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Trocador de Sódio e Cálcio/genética
Trocador de Sódio e Cálcio/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoproteins); 0 (Archaeal Proteins); 0 (Ligands); 0 (Peptide Fragments); 0 (Recombinant Proteins); 0 (Sodium-Calcium Exchanger); 9NEZ333N27 (Sodium); K848JZ4886 (Cysteine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.787168



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