Base de dados : MEDLINE
Pesquisa : D04.210.500.155.580.130.750.800 [Categoria DeCS]
Referências encontradas : 486 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 49 ir para página                         

  1 / 486 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26974139
[Au] Autor:Knittel DN; Lorenz P; Huber U; Stintzing FC; Kammerer DR
[Ti] Título:Characterization of the cardiac glycoside and lipid profiles of Strophanthus kombé Oliv. seeds.
[So] Source:Z Naturforsch C;71(3-4):55-64, 2016 Mar.
[Is] ISSN:0939-5075
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The seeds of Strophanthus kombé Oliv. are known to contain high levels of cardioactive compounds. However, the therapeutic use of Strophanthus in the treatment of cardiopathy requires more detailed knowledge of the compound profile to profit from the full potential of Strophanthus preparations. Therefore, the objective was to characterize the cardenolide profile and lipophilic constituents in S. kombé seeds using methods applicable in routine quality control. Freshly prepared S. kombé seed extracts were analyzed without previous sample clean-up using a novel HPLC-DAD-MSn method. In addition, seed oils were analyzed by GC-MS following derivatization of the lipids. More than 20 cardenolides were tentatively assigned in the seed extracts including strophanthidin, strophanthidol, periplogenin and strophanthidinic acid aglycones, carrying various saccharide moieties. The findings revealed the presence of eight novel cardenolides, which have not been described for S. kombé so far. The occurrence of strophanthidinic acid derivatives was verified by comparison with synthesized strophanthidinic acid-cymaropyranoside. GC-MS characterization of the oils mainly revealed the presence of fatty acids, especially oleic acid and linoleic acid, as well as phytosterols, the latter representing intermediates of cardenolide biosynthesis. In summary, these findings broaden our knowledge on the secondary metabolism of Strophanthus.
[Mh] Termos MeSH primário: Glicosídeos Cardíacos/análise
Lipídeos/análise
Sementes/química
Strophanthus/química
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Digitoxigenina/análogos & derivados
Digitoxigenina/análise
Ácidos Graxos/análise
Cromatografia Gasosa-Espectrometria de Massas
Ácido Linoleico/análise
Espectrometria de Massas
Estrutura Molecular
Ácido Oleico/análise
Fitosteróis/análise
Extratos Vegetais/química
Estrofantidina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiac Glycosides); 0 (Fatty Acids); 0 (Lipids); 0 (Phytosterols); 0 (Plant Extracts); 143-62-4 (Digitoxigenin); 2UMI9U37CP (Oleic Acid); 66-28-4 (Strophanthidin); 9KJL21T0QJ (Linoleic Acid); B6808P7IY9 (periplogenin)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170113
[Lr] Data última revisão:
170113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160315
[St] Status:MEDLINE


  2 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:24934035
[Au] Autor:Füessl HS; Stiefelhagen P
[Ti] Título:[Formerly this was almost the rule. Why are the elderly no longer receiving digitalis before an operation?].
[Ti] Título:Früher war das fast Gesetz. Warum werden Altere vor einer OP nicht mehr digitalisiert?.
[So] Source:MMW Fortschr Med;156(2):17, 2014 Feb 06.
[Is] ISSN:1438-3276
[Cp] País de publicação:Germany
[La] Idioma:ger
[Mh] Termos MeSH primário: Fibrilação Atrial/prevenção & controle
Glicosídeos Digitálicos/administração & dosagem
Indicadores Básicos de Saúde
Insuficiência Cardíaca/prevenção & controle
Cuidados Pré-Operatórios/normas
Estrofantidina/administração & dosagem
Taquicardia/prevenção & controle
[Mh] Termos MeSH secundário: Fatores Etários
Seres Humanos
Injeções Intravenosas
[Pt] Tipo de publicação:NEWS
[Nm] Nome de substância:
0 (Digitalis Glycosides); 66-28-4 (Strophanthidin)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:140617
[Lr] Data última revisão:
140617
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140618
[St] Status:MEDLINE


  3 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:23836687
[Au] Autor:Adachi N; Yoshida T; Nin F; Ogata G; Yamaguchi S; Suzuki T; Komune S; Hisa Y; Hibino H; Kurachi Y
[Ad] Endereço:H. Hibino: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata 951-8510, Japan. hibinoh@med.niigata-u.ac.jp Y. Kurachi: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. ykurachi@pharma2.med.osaka-u.ac.jp.
[Ti] Título:The mechanism underlying maintenance of the endocochlear potential by the K+ transport system in fibrocytes of the inner ear.
[So] Source:J Physiol;591(18):4459-72, 2013 Sep 15.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The endocochlear potential (EP) of +80 mV in the scala media, which is indispensable for audition, is controlled by K+ transport across the lateral cochlear wall. This wall includes two epithelial barriers, the syncytium and the marginal cells. The former contains multiple cell types, such as fibrocytes, which are exposed to perilymph on their basolateral surfaces. The apical surfaces of the marginal cells face endolymph. Between the two barriers lies the intrastrial space (IS), an extracellular space with a low K+ concentration ([K+]) and a potential similar to the EP. This intrastrial potential (ISP) dominates the EP and represents the sum of the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium and the syncytium's potential, which is slightly positive relative to perilymph. Although a K+ transport system in fibrocytes seems to contribute to the EP, the mechanism remains uncertain. We examined the electrochemical properties of the lateral wall of guinea pigs with electrodes sensitive to potential and K+ while perfusing into the perilymph of the scala tympani blockers of Na+,K+-ATPase, the K+ pump thought to be essential to the system. Inhibiting Na+,K+-ATPase barely affected [K+] in the IS but greatly decreased [K+] within the syncytium, reducing the K+ gradient across its apical surface. The treatment hyperpolarized the syncytium only moderately. Consequently, both the ISP and the EP declined. Fibrocytes evidently use the Na+,K+-ATPase to achieve local K+ transport, maintaining the syncytium's high [K+] that is crucial for the K+ diffusion underlying the positive ISP.
[Mh] Termos MeSH primário: Células Epiteliais/metabolismo
Potenciais da Membrana
Potássio/metabolismo
Rampa do Tímpano/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Epiteliais/fisiologia
Células Gigantes/metabolismo
Células Gigantes/fisiologia
Cobaias
Transporte de Íons
Ouabaína/farmacologia
Perilinfa/metabolismo
Rampa do Tímpano/citologia
Rampa do Tímpano/fisiologia
ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
ATPase Trocadora de Sódio-Potássio/metabolismo
Estrofantidina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
5ACL011P69 (Ouabain); 66-28-4 (Strophanthidin); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); RWP5GA015D (Potassium)
[Em] Mês de entrada:1404
[Cu] Atualização por classe:160210
[Lr] Data última revisão:
160210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130710
[St] Status:MEDLINE
[do] DOI:10.1113/jphysiol.2013.258046


  4 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23407962
[Au] Autor:Berret E; Nehmé B; Henry M; Toth K; Drolet G; Mouginot D
[Ad] Endereço:Axe Neurosciences du Centre de Recherche du Centre Hospitalier Université de Québec (CHUQ), Université Laval, Québec, QC, Canada G1V 4G2.
[Ti] Título:Regulation of central Na+ detection requires the cooperative action of the NaX channel and α1 Isoform of Na+/K+-ATPase in the Na+-sensor neuronal population.
[So] Source:J Neurosci;33(7):3067-78, 2013 Feb 13.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The median preoptic nucleus (MnPO) holds a strategic position in the hypothalamus. It is adjacent to the third ventricle; hence, it can directly access the ionic composition of the CSF. MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as central sensors of extracellular Na(+) concentration ([Na(+)](ext)). The mechanism underlying Na(+) sensing involves the atypical Na(+) channel, Na(X). Here we sought to determine whether Na(+) influx in Na(+) sensors is actively regulated via interaction with other membrane proteins involved in cellular Na(+) homeostasis, such as Na(+)/K(+)-ATPase. The Na(+)/K(+)-ATPase role was investigated using patch-clamp recordings in rat MnPO dissociated neurons. Na(+) current evoked with hypernatriuric solution was diminished in the absence of ATP/GTP, indicating that Na(+)/K(+)-ATPase play a central role in [Na(+)](ext) detection. Specific blockers of α1 and α3 isoforms of Na(+)/K(+)-ATPase, ouabain or strophanthidin, inhibited this Na(+) current. However, strophanthidin, which selectively blocks the α1 isoform, was more effective in blocking Na(+) current, suggesting that the Na(+)/K(+)-ATPase-α1 isoform is specifically involved in [Na(+)](ext) detection. Although strophanthidin did not alter either the membrane resistance or the Na(+) reversal potential, the conductance and the permeability of the Na(X) channel decreased significantly. Our results suggest that Na(+)/K(+)-ATPase interacts with the Na(X) channel and regulates the high [Na(+)](ext)-evoked Na(+) current via influencing the Na(+) influx rate. This study describes a novel intracellular regulatory pathway of [Na(+)](ext) detection in MnPO neurons. The α1 isoform of Na(+)/K(+)-ATPase acts as a direct regulatory partner of the Na(X) channel and influences Na(+) influx via controlling the Na(+) permeability of the channel.
[Mh] Termos MeSH primário: Neurônios/metabolismo
Canais de Sódio/fisiologia
ATPase Trocadora de Sódio-Potássio/metabolismo
Sódio/fisiologia
[Mh] Termos MeSH secundário: Algoritmos
Animais
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Inibidores Enzimáticos/farmacologia
Imuno-Histoquímica
Masculino
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Ouabaína/farmacologia
Técnicas de Patch-Clamp
Permeabilidade
Área Pré-Óptica/citologia
Área Pré-Óptica/metabolismo
Ratos
Ratos Wistar
Bloqueadores dos Canais de Sódio/farmacologia
Canais de Sódio/efeitos dos fármacos
ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
Estrofantidina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Sodium Channel Blockers); 0 (Sodium Channels); 5ACL011P69 (Ouabain); 66-28-4 (Strophanthidin); 9NEZ333N27 (Sodium); EC 3.6.1.- (Atp1a1 protein, rat); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130215
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.4801-12.2013


  5 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23219877
[Au] Autor:Tam YY; Chen S; Zaifman J; Tam YK; Lin PJ; Ansell S; Roberge M; Ciufolini MA; Cullis PR
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada. tam7@mail.ubc.ca
[Ti] Título:Small molecule ligands for enhanced intracellular delivery of lipid nanoparticle formulations of siRNA.
[So] Source:Nanomedicine;9(5):665-74, 2013 Jul.
[Is] ISSN:1549-9642
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Gene silencing activity of lipid nanoparticle (LNP) formulations of siRNA requires LNP surface factors promoting cellular uptake. This study aimed to identify small molecules that enhance cellular uptake of LNP siRNA systems, then use them as LNP-associated ligands to improve gene silencing potency. Screening the Canadian Chemical Biology Network molecules for effects on LNP uptake into HeLa cells found that cardiac glycosides like ouabain and strophanthidin caused the highest uptake. Cardiac glycosides stimulate endocytosis on binding to plasma membrane Na(+)/K(+) ATPase found in all mammalian cells, offering the potential to stimulate LNP uptake into various cell types. A PEG-lipid containing strophanthidin at the end of PEG (STR-PEG-lipid) was synthesized and incorporated into LNP. Compared to non-liganded systems, STR-PEG-lipid enhanced LNP uptake in various cell types. Furthermore, this enhanced uptake improved marker gene silencing in vitro. Addition of STR-PEG-lipid to LNP siRNA may have general utility for enhancing gene silencing potency. FROM THE CLINICAL EDITOR: In this study, the authors identified small molecules that enhance cellular uptake of lipid nanoparticle siRNA systems, then used them as LNP-associated ligands to improve gene silencing potency.
[Mh] Termos MeSH primário: Lipídeos/administração & dosagem
Nanopartículas/administração & dosagem
RNA Interferente Pequeno/genética
Estrofantidina/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Endocitose/genética
Inativação Gênica/efeitos dos fármacos
Técnicas de Transferência de Genes
Células HeLa
Seres Humanos
Ligantes
Lipídeos/química
Nanopartículas/química
RNA Interferente Pequeno/química
ATPase Trocadora de Sódio-Potássio/genética
ATPase Trocadora de Sódio-Potássio/metabolismo
Estrofantidina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ligands); 0 (Lipids); 0 (RNA, Small Interfering); 66-28-4 (Strophanthidin); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:130624
[Lr] Data última revisão:
130624
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121211
[St] Status:MEDLINE


  6 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:22773774
[Au] Autor:Wang YC; Yang JJ; Huang RC
[Ad] Endereço:Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
[Ti] Título:Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.
[So] Source:J Neurophysiol;108(7):2024-32, 2012 Oct.
[Is] ISSN:1522-1598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.
[Mh] Termos MeSH primário: Neurônios/fisiologia
ATPase Trocadora de Sódio-Potássio/metabolismo
Sódio/metabolismo
Núcleo Supraquiasmático/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Cianetos/farmacologia
Corantes Fluorescentes
Espaço Intracelular/metabolismo
Monensin/farmacologia
Potássio/metabolismo
Ratos
Ratos Sprague-Dawley
ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos
Estrofantidina/farmacologia
Tetrodotoxina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cyanides); 0 (Fluorescent Dyes); 4368-28-9 (Tetrodotoxin); 66-28-4 (Strophanthidin); 906O0YJ6ZP (Monensin); 9NEZ333N27 (Sodium); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); RWP5GA015D (Potassium)
[Em] Mês de entrada:1306
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120710
[St] Status:MEDLINE
[do] DOI:10.1152/jn.00361.2012


  7 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:22257758
[Au] Autor:Zhang LN; Su SW; Guo F; Guo HC; Shi XL; Li WY; Liu X; Wang YL
[Ad] Endereço:Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
[Ti] Título:Serotonin-mediated modulation of Na+/K+ pump current in rat hippocampal CA1 pyramidal neurons.
[So] Source:BMC Neurosci;13:10, 2012 Jan 19.
[Is] ISSN:1471-2202
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na+/K+ pump in rat hippocampal CA1 pyramidal neurons. RESULTS: 5-HT (0.1, 1 mM) showed Na+/K+ pump current (Ip) densities of 0.40 ± 0.04, 0.34 ± 0.03 pA/pF contrast to 0.63 ± 0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT3 receptor (5-HT3R) antagonist, not by WAY100635, a 5-HT1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT3R specific agonist, mimicked the effect of 5-HT on Ip. CONCLUSION: 5-HT inhibits neuronal Na+/K+ pump activity via 5-HT3R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.
[Mh] Termos MeSH primário: Região CA1 Hipocampal/citologia
Células Piramidais/efeitos dos fármacos
Serotonina/farmacologia
ATPase Trocadora de Sódio-Potássio/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Biguanidas/farmacologia
Biofísica
Relação Dose-Resposta a Droga
Estimulação Elétrica
Técnicas In Vitro
Inibição Neural/efeitos dos fármacos
Técnicas de Patch-Clamp
Piperazinas/farmacologia
Células Piramidais/fisiologia
Piridinas/farmacologia
Ratos
Ratos Sprague-Dawley
Antagonistas da Serotonina/farmacologia
Agonistas de Receptores de Serotonina/farmacologia
Bloqueadores dos Canais de Sódio/farmacologia
Estrofantidina/farmacologia
Tetrodotoxina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biguanides); 0 (Piperazines); 0 (Pyridines); 0 (Serotonin Antagonists); 0 (Serotonin Receptor Agonists); 0 (Sodium Channel Blockers); 333DO1RDJY (Serotonin); 4368-28-9 (Tetrodotoxin); 66-28-4 (Strophanthidin); 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide); 910A4X901V (1-(3-chlorophenyl)biguanide); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[Em] Mês de entrada:1206
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120120
[St] Status:MEDLINE
[do] DOI:10.1186/1471-2202-13-10


  8 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:21221670
[Au] Autor:Rogers JT; Mikkilineni S; Cantuti-Castelvetri I; Smith DH; Huang X; Bandyopadhyay S; Cahill CM; Maccecchini ML; Lahiri DK; Greig NH
[Ad] Endereço:Neurochemistry Laboratory, Psychiatry-Neuroscience, Massachusetts General Hospital, Charlestown, MA 02129, USA. Jrogers@partners.org
[Ti] Título:The alpha-synuclein 5'untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen.
[So] Source:J Neural Transm (Vienna);118(3):493-507, 2011 Mar.
[Is] ISSN:1435-1463
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Increased brain α-synuclein (SNCA) protein expression resulting from gene duplication and triplication can cause a familial form of Parkinson's disease (PD). Dopaminergic neurons exhibit elevated iron levels that can accelerate toxic SNCA fibril formation. Examinations of human post mortem brain have shown that while mRNA levels for SNCA in PD have been shown to be either unchanged or decreased with respect to healthy controls, higher levels of insoluble protein occurs during PD progression. We show evidence that SNCA can be regulated via the 5'untranslated region (5'UTR) of its transcript, which we modeled to fold into a unique RNA stem loop with a CAGUGN apical loop similar to that encoded in the canonical iron-responsive element (IRE) of L- and H-ferritin mRNAs. The SNCA IRE-like stem loop spans the two exons that encode its 5'UTR, whereas, by contrast, the H-ferritin 5'UTR is encoded by a single first exon. We screened a library of 720 natural products (NPs) for their capacity to inhibit SNCA 5'UTR driven luciferase expression. This screen identified several classes of NPs, including the plant cardiac glycosides, mycophenolic acid (an immunosuppressant and Fe chelator), and, additionally, posiphen was identified to repress SNCA 5'UTR conferred translation. Western blotting confirmed that Posiphen and the cardiac glycoside, strophanthidine, selectively blocked SNCA expression (~1 µM IC(50)) in neural cells. For Posiphen this inhibition was accelerated in the presence of iron, thus providing a known APP-directed lead with potential for use as a SNCA blocker for PD therapy. These are candidate drugs with the potential to limit toxic SNCA expression in the brains of PD patients and animal models in vivo.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Encéfalo/metabolismo
Cardenolídeos/farmacologia
Dicloxacilina/farmacologia
Ferro/metabolismo
Emaranhados Neurofibrilares/metabolismo
Estrofantidina/farmacologia
alfa-Sinucleína/metabolismo
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas/genética
Western Blotting
Encéfalo/patologia
Linhagem Celular Tumoral
Células Cultivadas
Seres Humanos
Emaranhados Neurofibrilares/efeitos dos fármacos
Emaranhados Neurofibrilares/genética
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Neurônios/patologia
Biossíntese de Proteínas/efeitos dos fármacos
Biossíntese de Proteínas/fisiologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
alfa-Sinucleína/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Anti-Bacterial Agents); 0 (Cardenolides); 0 (RNA, Messenger); 0 (SNCA protein, human); 0 (alpha-Synuclein); 66-28-4 (Strophanthidin); COF19H7WBK (Dicloxacillin); E1UOL152H7 (Iron); G36K2H8SME (gitoxigenin)
[Em] Mês de entrada:1108
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110112
[St] Status:MEDLINE
[do] DOI:10.1007/s00702-010-0513-5


  9 / 486 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:19171658
[Au] Autor:Del Negro CA; Kam K; Hayes JA; Feldman JL
[Ad] Endereço:Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA. cadeln@wm.edu
[Ti] Título:Asymmetric control of inspiratory and expiratory phases by excitability in the respiratory network of neonatal mice in vitro.
[So] Source:J Physiol;587(Pt 6):1217-31, 2009 Mar 15.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rhythmic motor behaviours consist of alternating movements, e.g. swing-stance in stepping, jaw opening and closing during chewing, and inspiration-expiration in breathing, which must be labile in frequency, and in some cases, in the duration of individual phases, to adjust to physiological demands. These movements are the expression of underlying neural circuits whose organization governs the properties of the motor behaviour. To determine if the ability to operate over a broad range of frequencies in respiration is expressed in the rhythm generator, we isolated the kernel of essential respiratory circuits using rhythmically active in vitro slices from neonatal mice. We show respiratory motor output in these slices at very low frequencies (0.008 Hz), well below the typical frequency in vitro (approximately 0.2 Hz) and in most intact normothermic mammals. Across this broad range of frequencies, inspiratory motor output bursts remained remarkably constant in pattern, i.e. duration, peak amplitude and area. The change in frequency was instead attributable to increased interburst interval, and was largely unaffected by removal of fast inhibitory transmission. Modulation of the frequency was primarily achieved by manipulating extracellular potassium, which significantly affects neuronal excitability. When excitability was lowered to slow down, or in some cases stop, spontaneous rhythm, brief stimulation of the respiratory network with a glutamatergic agonist could evoke (rhythmic) motor output. In slices with slow (<0.02 Hz) spontaneous rhythms, evoked motor output could follow a spontaneous burst at short (60 s. We observed during inspiration a large magnitude (approximately 0.6 nA) outward current generated by Na(+)/K(+) ATPase that deactivated in 25-100 ms and thus could contribute to burst termination and the latency of evoked bursts but is unlikely to control the interburst interval. We propose that the respiratory network functions over a broad range of frequencies by engaging distinct mechanisms from those controlling inspiratory duration and pattern that specifically govern the interburst interval.
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Expiração/fisiologia
Inalação/fisiologia
Neurônios Motores/fisiologia
Centro Respiratório/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Animais Recém-Nascidos
Encéfalo/efeitos dos fármacos
Encéfalo/fisiologia
Técnicas In Vitro
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Neurônios Motores/efeitos dos fármacos
Técnicas de Patch-Clamp
Picrotoxina/farmacologia
Potássio/farmacologia
Centro Respiratório/efeitos dos fármacos
Estrofantidina/farmacologia
Estricnina/farmacologia
Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
124-87-8 (Picrotoxin); 66-28-4 (Strophanthidin); 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid); H9Y79VD43J (Strychnine); RWP5GA015D (Potassium)
[Em] Mês de entrada:0905
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:090128
[St] Status:MEDLINE
[do] DOI:10.1113/jphysiol.2008.164079


  10 / 486 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:18954525
[Au] Autor:Qi YJ; Su SW; Li JX; Li JH; Guo F; Wang YL
[Ad] Endereço:Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
[Ti] Título:Different Na+/K+-ATPase signal pathways was involved in the increase of [Ca2+]i induced by strophanthidin in normal and failing isolated guinea pig ventricular myocytes.
[So] Source:Acta Pharmacol Sin;29(11):1313-8, 2008 Nov.
[Is] ISSN:1745-7254
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str). METHODS: A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 micromol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 micromol/L Str-only group by a video-based, motion-edge detection system. RESULTS: Str at 1, 10, and 25 micromol/L in NC and Str at 0.1, 1, 10, and 25 micromol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC. CONCLUSION: The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.
[Mh] Termos MeSH primário: Cálcio/farmacologia
Miócitos Cardíacos/metabolismo
Transdução de Sinais/fisiologia
ATPase Trocadora de Sódio-Potássio/fisiologia
Estrofantidina/farmacologia
[Mh] Termos MeSH secundário: Animais
Cobaias
Insuficiência Cardíaca/tratamento farmacológico
Insuficiência Cardíaca/fisiopatologia
Ventrículos do Coração/citologia
Ventrículos do Coração/efeitos dos fármacos
Técnicas In Vitro
Masculino
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Proteínas Quinases Ativadas por Mitógeno/fisiologia
Contração Miocárdica/efeitos dos fármacos
Miócitos Cardíacos/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
66-28-4 (Strophanthidin); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:0904
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:081029
[St] Status:MEDLINE
[do] DOI:10.1111/j.1745-7254.2008.00897.x



página 1 de 49 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