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1.
J Lipid Res ; 63(6): 100220, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35490741

RESUMO

The localization of many membrane proteins within cholesterol- and sphingolipid-containing microdomains is essential for proper cell signaling and function. These membrane domains, however, are too small and dynamic to be recorded, even with modern super-resolution techniques. Therefore, the association of membrane proteins with these domains can only be detected with biochemical assays that destroy the integrity of cells require pooling of many cells and take a long time to perform. Here, we present a simple membrane fluidizer-induced clustering approach to identify the phase-preference of membrane-associated molecules in individual live cells within 10-15 min. Experiments in phase-separated bilayers and live cells on molecules with known phase preference show that heptanol hyperfluidizes the membrane and stabilizes phase separation. This results in a transition from nanosized to micronsized clusters of associated molecules allowing their identification using routine microscopy techniques. Membrane fluidizer-induced clustering is an inexpensive and easy to implement method that can be conducted at large-scale and allows easy identification of protein partitioning in live cell membranes.


Assuntos
Colesterol , Microdomínios da Membrana , Membrana Celular/química , Colesterol/metabolismo , Heptanol/análise , Heptanol/metabolismo , Bicamadas Lipídicas/metabolismo , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/metabolismo
2.
J Agric Food Chem ; 70(15): 4712-4724, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35380838

RESUMO

The heterocyclic compounds 2,6-dimethyl-4-propyl-1,3-oxathiane 1 and 2,4-dimethyl-6-propyl-1,3-oxathiane 2 were obtained by condensing 4-mercapto-2-heptanol and 2-mercapto-4-heptanol, respectively, with acetaldehyde. For both, separation of the eight stereoisomers was achieved via capillary gas chromatography using heptakis(diethyl-tert-butyldimethylsilyl)-ß-cyclodextrin as the chiral stationary phase. Their configurations were assigned by combinations of enzyme-catalyzed kinetic resolutions, HPLC separations, and assessments of NMR data. The odor thresholds and odor qualities of the stereoisomers were determined by capillary gas chromatography/olfactometry. The odor thresholds of the stereoisomers of 2 were generally higher than those of 1. For both oxathianes, the stereoisomers in which all substituents are in equatorial positions showed the highest odor thresholds. Most of the stereoisomers of 1 exhibited pleasant flowery, fruity, or sweet nuances; the stereoisomers of 2 were mainly characterized by descriptors, such as broth, mushroom, or pungent. The data demonstrate the impact of the positions of substituents and their spatial orientations on the sensory properties of 1,3-oxathianes.


Assuntos
Odorantes , Heptanol , Compostos Heterocíclicos com 1 Anel , Odorantes/análise , Olfatometria , Estereoisomerismo
4.
J Am Chem Soc ; 144(9): 4047-4056, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35073694

RESUMO

Petroleum hydrocarbons are our major energy source and an important feedstock for the chemical industry. With the exception of combustion, the deep conversion of chemically inert hydrocarbons to more valuable chemicals is of considerable interest. However, two challenges hinder this conversion. One is the regioselective activation of inert carbon-hydrogen (C-H) bonds. The other is designing a pathway to realize this complicated conversion. In response to the two challenges, a multistep bioelectrocatalytic system was developed to realize the one-pot deep conversion from heptane to N-heptylhepan-1-imine under mild conditions. First, in this enzymatic cascade, a bioelectrocatalytic C-H bond oxyfunctionalization step based on alkane hydroxylase (alkB) was applied to regioselectively convert heptane to 1-heptanol. By integrating subsequent alcohol oxidation and bioelectrocatalytic reductive amination steps based on an engineered choline oxidase (AcCO6) and a reductive aminase (NfRedAm), the generated 1-heptanol was successfully converted to N-heptylhepan-1-imine. The electrochemical architecture provided sufficient electrons to drive the bioelectrocatalytic C-H bond oxyfunctionalization and reductive amination steps with neutral red (NR) as electron mediator. The highest concentration of N-heptylhepan-1-imine achieved was 0.67 mM with a Faradaic efficiency of 45% for C-H bond oxyfunctionalization and 70% for reductive amination. Hexane, octane, and ethylbenzene were also successfully converted to the corresponding imines. Via regioselective C-H bond oxyfunctionalization, intermediate oxidation, and reductive amination, the bioelectrocatalytic hydrocarbon deep conversion system successfully realized the challenging conversion from inert hydrocarbons to imines that would have been impossible by using organic synthesis methods and provided a new methodology for the comprehensive conversion and utilization of inert hydrocarbons.


Assuntos
Hidrocarbonetos , Iminas , Aminação , Heptanos , Heptanol , Iminas/química
5.
Int J Biol Macromol ; 193(Pt A): 672-680, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34710478

RESUMO

In this study, we investigated the interaction between myofibrillar proteins (MPs) and selected alcohols (1-pentanol, 1-hexanol, and 1-heptanol). Only 1-heptanol exhibited the binding ability to MPs, and the binding ability significantly increased with increasing protein concentration (p < 0.05). In addition, both static and dynamic quenching occurred during the interaction, with a red shift of the maximum absorption peak in the synchronous fluorescence spectra indicating a change in the microenvironment of the MPs. The results of circular dichroism measurements suggested that the interaction between MPs and 1-heptanol altered the secondary structure of the MPs. Furthermore, thermodynamic analysis showed that hydrogen bonding and van der Waals forces dominated the interaction between MPs and 1-heptanol, which was confirmed by the results of molecular docking/dynamics simulations. This study provides an in-depth understanding of the interaction between MPs and alcohols, which can help to improve the flavor control in meat.


Assuntos
Proteínas de Transporte/química , Heptanol/química , Simulação de Acoplamento Molecular , Proteínas Musculares/química , Miofibrilas/química , Sítios de Ligação , Fenômenos Biofísicos , Dicroísmo Circular , Fluorescência , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Termodinâmica
6.
Plant Cell Environ ; 44(8): 2700-2715, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33866575

RESUMO

Plant viruses can manipulate their hosts to release odours that are attractive or repellent to their insect vectors. However, the volatile organic compounds (VOCs), either individually or as mixtures, which play a key role in the olfactory behaviour of insect vectors remains largely unknown. Our study focused on green rice leafhoppers (GRLHs) vectoring rice dwarf virus (RDV) revealed that RDV infection significantly induced the emission of (E)-ß-caryophyllene and 2-heptanol by rice plants, which influenced the olfactory behaviour of both non-viruliferous and viruliferous GRLHs. (E)-ß-caryophyllene attracted non-viruliferous GRLHs to settle on RDV-infected plants, but neither attracted nor repelled viruliferous GRLHs. In contrast, 2-heptanol repelled viruliferous GRLHs to settle on RDV-infected plants, but neither repelled nor attracted non-viruliferous GRLHs. Suppression of (E)-ß-caryophyllene synthase OsCAS via CRISPR-Cas9 to generate oscas-1 plants enabled us to confirm the important role played by (E)-ß-caryophyllene in modulating the virus-vector-host plant interaction. These novel results reveal the role of these virus-induced VOCs in modulating the behaviour of its GRLH insect vector and may facilitate the design of new strategies for disease control through manipulation of plant volatile emissions.


Assuntos
Hemípteros/efeitos dos fármacos , Interações Hospedeiro-Patógeno/fisiologia , Oryza/virologia , Reoviridae/patogenicidade , Compostos Orgânicos Voláteis/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Enzimas/genética , Enzimas/metabolismo , Regulação da Expressão Gênica de Plantas , Hemípteros/fisiologia , Heptanol/metabolismo , Heptanol/farmacologia , Repelentes de Insetos/metabolismo , Repelentes de Insetos/farmacologia , Odorantes , Oryza/genética , Oryza/metabolismo , Doenças das Plantas/virologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Vírus de Plantas/patogenicidade , Plantas Geneticamente Modificadas , Sesquiterpenos Policíclicos/metabolismo , Compostos Orgânicos Voláteis/farmacologia
7.
J Chem Ecol ; 47(2): 167-174, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33475941

RESUMO

The study of insect semiochemicals, especially pheromones, is of fundamental importance for the development of strategies for controlling agricultural pests. In this study, volatile compounds involved in the communication between males and females of the fruit fly, Anastrepha obliqua (Diptera: Tephritidae), for mating purposes were characterized to develop attractant formulations for females of this species. Extracts containing volatile compounds released by males of A. obliqua were obtained by the dynamic headspace technique and analyzed by gas chromatography coupled with an electroantennographic detector (GC-EAD) and gas chromatography coupled with mass spectrometry (GC-MS). Twenty-one volatile compounds were identified in the aeration extracts of males. Five of them caused EAD responses from the antennae of females: 1-heptanol, linalool, (Z)-3-nonen-1-ol, (E,Z)-3,6-nonadien-1-ol, and (Z,E)-α-farnesene. Six synthetic mixtures of these compounds, including the five-component blend and all possible four-component blends, were formulated in a biopolymer and used in behavioral bioassays conducted in the laboratory arena with conspecific virgin females. One blend of 1-heptanol, linalool, (Z)-3-nonen-1-ol, and (Z,E)-α-farnesene attracted more females than the collection of volatiles from virgin males used as control. The other mixtures were as attractive to A. obliqua females as the control treatment. This study indicates potential for use of these compounds in monitoring and control strategies for this pest.


Assuntos
Monoterpenos Acíclicos/isolamento & purificação , Heptanol/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Atrativos Sexuais/fisiologia , Tephritidae/fisiologia , Animais , Antenas de Artrópodes/fisiologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Atrativos Sexuais/química , Tephritidae/química
8.
Chem Senses ; 45(7): 513-521, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32609815

RESUMO

Probing the neural mechanisms that underlie each sensory system requires the presentation of perceptually appropriate stimulus concentrations. This is particularly relevant in the olfactory system as additional odorant receptors typically respond with increasing stimulus concentrations. Thus, perceptual measures of olfactory sensitivity provide an important guide for functional experiments. This study focuses on aliphatic alcohols because they are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination, and assess odor-structure activity relationships in mice. However, despite their frequent use, a systematic study of the relative sensitivity of these odorants in mice is not available. Thus, we assayed the ability of C57BL/6J mice to detect a homologous series of primary aliphatic alcohols (1-propanol to 1-heptanol) using a head-fixed Go/No-Go operant conditioning assay combined with highly reproducible stimulus delivery. To aid in the accessibility of our data, we report the animal's threshold to each odorant according to the 1) ideal gas condition, 2) nonideal gas condition (factoring in the activity of the odorant in the solvent), and 3) the liquid dilution of the odorant in the olfactometer. Of the odorants tested, mice were most sensitive to 1-hexanol and least sensitive to 1-butanol. These updated measures of murine sensitivity will hopefully guide experimenters in choosing appropriate stimulus concentrations for experiments using these odorants.


Assuntos
Álcoois Graxos/química , Limiar Sensorial/fisiologia , Olfato/fisiologia , 1-Butanol/química , 1-Butanol/farmacologia , 1-Propanol/química , 1-Propanol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Álcoois Graxos/farmacologia , Feminino , Gases/química , Heptanol/química , Heptanol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Limiar Sensorial/efeitos dos fármacos
9.
PLoS One ; 15(5): e0233094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392267

RESUMO

Sweet corn juice is becoming increasingly popular in China. In order to provide valuable health-related information to consumers, the nutritional and physicochemical characteristics of raw and boiled purple sweet corn juices were herein investigated. Sugars, antinutrients, total free phenols, anthocyanins, and antioxidant activity were analyzed by conventional chemical methods. The viscosity and stability of juices were determined by Ubbelohde viscosity meter and centrifugation, respectively. Boiling process could elevate viscosity, stability and sugar content, and reduce antinutrients, total free phenols, anthocyanins, and antioxidant activity in corn juice. In addition, short time boiling efficiently reduced the degradation of anthocyanins during subsequent refrigeration. The content of amino acids, vitamin B1/B2 and E were detected by High Performance Liquid Chromatography. Gas Chromatography Mass Spectrometry was used for the analysis of fatty acids and aroma compounds. Several aroma compounds not previously reported in corn were identified, including 1-heptanol, 2-methyl-2-butenal, (Z)-3-nonen-1-ol, 3-ethyl-2-methyl-1,3-hexadiene, and 2,4-bis(1,1-dimethylethyl)phenol. Interestingly, the boiling process had no apparent effect on the amino acids profile, but it caused a 45.8% loss of fatty acids in the juice by promoting the retention of fatty acids in the corn residue. These results provide detailed information that could be used for increasing consumers' knowledge of sweet corn juice, further development of sweet corn juice by food producers, and maize breeding programs.


Assuntos
Zea mays/química , Aldeídos/análise , Aminoácidos/análise , Antocianinas/análise , Antioxidantes/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Heptanol/análise , Fenóis/análise , Extratos Vegetais/análise , Riboflavina/análise , Tiamina/análise
10.
Cardiovasc Res ; 116(13): 2081-2090, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031595

RESUMO

AIMS: Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia. METHODS AND RESULTS: Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia. Ventricular activation was unchanged at 31°C while action potential duration (APD) was significantly prolonged (176.9 ± 4.2 ms vs. 241.0 ± 2.9 ms, P < 0.05), as was ventricular repolarization. At 17°C, there were proportionally similar delays in both activation and repolarization. These changes were reflected in the QRS and QT intervals of ECG recordings. Ventricular fibrillation threshold was significantly reduced at 31°C (16.3 ± 3.1 vs. 35 ± 3.5 mA, P < 0.05) but increased at 17°C (64.2 ± 9.9, P < 0.05). At 31°C, transverse conduction was relatively unchanged by cooling compared to longitudinal conduction, but at 17°C both transverse and longitudinal conduction were proportionately reduced to a similar extent. The gap junction uncoupler heptanol had a larger relative effect on transverse than longitudinal conduction and was able to restore the transverse/longitudinal conduction ratio, returning ventricular fibrillation threshold to baseline values (16.3 ± 3.1 vs. 36.3 ± 4.3 mA, P < 0.05) at 31°C. Rewarming to 37°C restored the majority of the electrophysiological parameters. CONCLUSIONS: Moderate hypothermia does not significantly change ventricular conduction time but prolongs repolarization and is pro-arrhythmic. Further cooling to severe hypothermia causes parallel changes in ventricular activation and repolarization, changes which are anti-arrhythmic. Therefore, relative changes in QRS and QT intervals (QR/QTc) emerge as an ECG-biomarker of pro-arrhythmic activity. Risk for ventricular fibrillation appears to be linked to the relatively low temperature sensitivity of ventricular transmural conduction, a conclusion supported by the anti-arrhythmic effect of heptanol at 31°C.


Assuntos
Potenciais de Ação , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Hipotermia Induzida/efeitos adversos , Hipotermia/complicações , Fibrilação Ventricular/etiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Regulação da Temperatura Corporal , Simulação por Computador , Modelos Animais de Doenças , Eletrocardiografia , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Heptanol/farmacologia , Hipotermia/fisiopatologia , Hipotermia/terapia , Preparação de Coração Isolado , Modelos Cardiovasculares , Coelhos , Reaquecimento , Fatores de Tempo , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapia , Imagens com Corantes Sensíveis à Voltagem
11.
J Biol Chem ; 294(44): 16164-16171, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31511325

RESUMO

The self-labeling protein HaloTag has been used extensively to determine the localization and turnover of proteins of interest at the single-cell level. To this end, halogen-substituted alkanes attached to diverse fluorophores are commercially available that allow specific, irreversible labeling of HaloTag fusion proteins; however, measurement of protein of interest half-life by pulse-chase of HaloTag ligands is not widely employed because residual unbound ligand continues to label newly synthesized HaloTag fusions even after extensive washing. Excess unlabeled HaloTag ligand can be used as a blocker of undesired labeling, but this is not economical. In this study, we screened several inexpensive, low-molecular-weight haloalkanes as blocking agents in pulse-chase labeling experiments with the cell-permeable tetramethylrhodamine HaloTag ligand. We identified 7-bromoheptanol as a high-affinity, low-toxicity HaloTag-blocking agent that permits protein turnover measurements at both the cell population (by blotting) and single-cell (by imaging) levels. We show that the HaloTag pulse-chase approach is a nontoxic alternative to inhibition of protein synthesis with cycloheximide and extend protein turnover assays to long-lived proteins.


Assuntos
Bioensaio/métodos , Análise de Célula Única/métodos , Coloração e Rotulagem/métodos , Corantes Fluorescentes/metabolismo , Meia-Vida , Heptanol/análogos & derivados , Heptanol/química , Ligantes , Estabilidade Proteica , Proteínas , Proteólise , Rodaminas/química , Rodaminas/metabolismo
12.
Food Res Int ; 123: 298-310, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31284980

RESUMO

The characteristic volatile profile of the Spanish Vinagre de Jerez (VJ), Vinagre de Condado de Huelva (VC) and Vinagre de Montilla-Moriles (VMM) protected designation of origin (PDO) wine vinegars has been studied and compared for the first time by headspace stir bar sorptive extraction-gas chromatography-mass spectrometry (HSSE-GC-MS). The possible markers of each category and PDO were assessed. Acetates were the majority group in all vinegars, while ketones, C13-norisoprenoids and volatile phenols showed significant differences between the three PDOs. Analysis of variance (ANOVA), heatmap and partial least squares-discriminant analysis (PLS-DA) were performed. According to these results, 1-heptanol, methyl nonanoate, 2-methylbutanoic acid, 2,2,6-trimethyl-cyclohexanone, trans-2-decenal, eucalyptol and α-terpineol, were the most significant compounds for differentiating of VC, diacetyl and acetoin, ethyl 3-ethoxypropanoate, 2- and 3-heptanone, 2-methyl-1-hexadecanol, 1-octen-3-ol, p-Cresol and camphene for VMM; and ß-damascenone, 5-hydroxymethylfurfural, 3-heptanol, trans-2-hexen-1-ol and trans-2-hexen-1-yl acetate for VJ. Classification results showed that 100% of PDO samples were correctly classified, reaffirming the utility of the volatile profiles for classifying and authenticating wine vinegar PDOs.


Assuntos
Ácido Acético/análise , Compostos Orgânicos Voláteis/análise , Vinho/análise , Monoterpenos Bicíclicos/análise , Butiratos/análise , Cresóis/análise , Monoterpenos Cicloexânicos/análise , Análise Discriminante , Eucaliptol/análise , Manipulação de Alimentos , Furaldeído/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas , Heptanol/análise , Cetonas/análise , Norisoprenoides , Sensibilidade e Especificidade
13.
Food Chem ; 289: 645-656, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955659

RESUMO

We investigated the dynamic changes in norisoprenoids and phenylalanine derivatives in off-vine Vidal blanc. Glycosidically bound as well as free-form volatile compounds were identified by GC-MS in two vintages. Thus, off-vine grape exhibited the development of four higher alcohols (viz. linalool oxide, 2-octanol, 1-pentanol, and 1-heptanol), C13-norisoprenoids (α-ionone), phenylalanine-derivates (2-phenylethanol), whereas ß-ionone and geranial showed high correlation in on-vine grape. Freeze-thaw cycles and desiccation, two exterior stress affect volatile compound development, resulted in content fluctuations during late harvest. Interestingly, the total content of higher alcohols was higher in on-vine grapes than off-vine grapes in two vintages respectively. Interestingly, the content of higher alcohols was higher in off-vine samples in the 2016 and 2017 vintages. In terms of physicochemical parameters, off-vine Vidal showed results similar to those of on-vine sample. Nevertheless, sensorial impression of the grape juice was influenced by interaction of vintages and vine treatments.


Assuntos
Norisoprenoides/análise , Fenilalanina/análise , Vitis/química , Compostos Orgânicos Voláteis/análise , Monoterpenos Acíclicos , Álcoois/análise , Carotenoides/análise , Análise por Conglomerados , Cicloexanóis/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Heptanol/análise , Humanos , Masculino , Monoterpenos/análise , Octanóis/análise , Pentanóis/análise , Paladar , Compostos de Tritil/análise , Vinho/análise
14.
Glia ; 67(5): 791-801, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30715764

RESUMO

Peripheral sensory ganglia contain the somata of neurons mediating mechanical, thermal, and painful sensations from somatic, visceral, and oro-facial organs. Each neuronal cell body is closely surrounded by satellite glial cells (SGCs) that have properties and functions similar to those of central astrocytes, including expression of gap junction proteins and functional dye coupling. As shown in other pain models, after systemic pain induction by intra-peritoneal injection of lipopolysaccharide, dye coupling among SGCs in intact trigeminal ganglion was enhanced. Moreover, neuron-neuron and neuron-SGC coupling was also detected. To verify the presence of gap junction-mediated coupling between SGCs and sensory neurons, we performed dual whole cell patch clamp recordings from both freshly isolated and short term cultured cell pairs dissociated from mouse trigeminal ganglia. Bidirectional gap junction mediated electrical responses were frequently recorded between SGCs, between neurons and between neurons and SGCs. Polarization of SGC altered neuronal excitability, providing evidence that gap junction-mediated interactions between neurons and glia within sensory ganglia may contribute to integration of peripheral sensory responses, and to the modulation and coordinaton of neuronal activity.


Assuntos
Junções Comunicantes/fisiologia , Neuroglia/fisiologia , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Gânglio Trigeminal/citologia , Animais , Compostos de Boro/farmacologia , Carbenoxolona/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Ácido Flufenâmico/farmacologia , Junções Comunicantes/efeitos dos fármacos , Heptanol/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Isoquinolinas/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Probenecid/farmacologia , Transmissão Sináptica/efeitos dos fármacos
15.
Heart Vessels ; 34(6): 1052-1063, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30604190

RESUMO

It has been demonstrated that S1P receptors affect heart ischaemia-reperfusion (IR) induced injury. However, whether S1P receptors affect IR-induced cardiac death has not been investigated. The aim of this paper is to demonstrate the role of S1P receptors in IR-induced cardiac death. Healthy adult male Sprague-Dawley rats were assigned to the following groups: non-operation control group, sham operation group, IR group, IR group pretreated with DMSO, IR group pretreated with S1P3 agonist, IR group pretreated with an antagonist of S1P3, IR group pretreated with S1P2 and S1P3 antagonists, IR group pretreated with heptanol and antagonists of S1P2/3, and IR group pretreated with Gap26 and antagonists of S1P2/3 (heptanol acts as a Cx43 uncoupler and the mimic peptide Gap26 as Cx43 blocker). The groups with S1P2 or S1P3 agonist application before reperfusion were used to assess whether these can be used for therapy of IR. The haemodynamics, electrocardiograms (ECG), infarction area, and mortality rates were recorded. Immunohistological connexin 43 (Cx43) expression in the heart was detected in each group. Blocking S1P2/3 receptors with specific antagonists resulted in an increment of IR-induced mortality, increased infarction size, redistribution of Cx43 expression, as well as affecting the heart function. The infarction size, heart function, and mortality were totally or partially restored in the S1P2, S1P3 agonist-pretreated IR group, and the heptanol/Gap26-treated S1P2/3-blocked IR group. The S1P receptor S1P2/3 and Cx43 are involved in the IR-induced cardiac death.


Assuntos
Morte Súbita Cardíaca/prevenção & controle , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Peptídeos/farmacologia , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Conexina 43/antagonistas & inibidores , Conexina 43/metabolismo , Morte Súbita Cardíaca/etiologia , Heptanol/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Lisoesfingolipídeo/agonistas , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Receptores de Esfingosina-1-Fosfato
16.
J Sep Sci ; 42(2): 566-573, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30371989

RESUMO

In this study, the application of a mixture of organic solvents as a supported liquid membrane for improving the efficiency of the electromembrane extraction procedure was investigated. The extraction process was followed by high-performance liquid chromatography analysis of two model drugs (verapamil and riluzole). In this research, four organic solvents, including 1-heptanol, 1-octanol, 2-nitrophenyl octyl ether, and 2-ethyl hexanol, were selected as model solvents and different binary mixtures (v/v 2:1, 1:1 and 1:2) were used as the supported liquid membrane. The mixture of 2-ethyl hexanol and 1-otanol (v/v, 2:1) improved the extraction efficiency of model drugs by 1.5 to 12 times. It was found that extraction efficiency is greatly influenced by the level of electric current. In this study, for various mixtures of organic solvents, the electric current fluctuated between 50 and 2500 µA, and the highest extraction efficiencies were obtained with low and stable electric currents. Finally, the optimized extraction condition was validated and applied for the determination of model drugs in urine and wastewater samples.


Assuntos
Técnicas Eletroquímicas , Riluzol/isolamento & purificação , Verapamil/isolamento & purificação , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , 1-Octanol/química , Éteres/química , Heptanol/química , Hexanóis/química , Riluzol/química , Riluzol/urina , Solventes/química , Verapamil/química , Verapamil/urina , Poluentes Químicos da Água/química , Poluentes Químicos da Água/urina
17.
Toxicol In Vitro ; 51: 136-144, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29778719

RESUMO

In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias. These substances influence sodium, calcium, and potassium channels, but the complete mechanism of action of heptanol and ethanol remains unknown. The optical mapping method was used to measure conduction velocities (CVs) in concentrations of 0.05-1.8 mM heptanol and 17-1342 mM ethanol. Heptanol was shown to slow the excitation wave significantly, and a mechanism that involves a simultaneous action on cell coupling and activation threshold was suggested. Whole-cell patch-clamp experiments showed inhibition of sodium and calcium currents at a concentration of 0.5 mM heptanol. Computer modeling was used to estimate the relative contribution of the cell uncoupling and activation threshold increase caused by heptanol. Unlike heptanol, ethanol slightly influenced the CV at clinically relevant concentrations. Additionally, the critical concentrations for re-entry formation in ethanol were determined.


Assuntos
Etanol/farmacologia , Heptanol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Ventrículos do Coração , Miócitos Cardíacos/fisiologia , Ratos Sprague-Dawley
18.
Toxicol Lett ; 298: 81-90, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29601860

RESUMO

A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal exposure were analysed to investigate the suitability of selected metabolites to reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19-38 years, median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot urine samples of the volunteers, collected before exposure and during the following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2,5-dione, 1-ol, 2-ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre-exposure concentrations between <0.5 (3-one) and 82.9 µg/L (4-one), exposure increased the concentrations for all parameters except for 4-one. Median post-exposure concentrations ranged up to 840.4 µg/L (2-ol) and decreased with half-lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05) revealed weak to moderate associations of volume related metabolite excretion with external exposure for 2-one, 3-one and 2,5-dione (R = 0.332-0.753). Heptanol excretion was moderately associated with exposure (R ≥ 0.509) only after creatinine adjustment. Lacking association with external exposure impedes the use of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive indicators of exposure if creatinine correction is applied. By providing fundamental data on a panel of eight potential heptane metabolites, our study can help to promote biological monitoring of n-heptane exposure.


Assuntos
Heptanos/urina , Heptanol/urina , Cetonas/urina , Eliminação Renal , Adulto , Biotransformação , Biomarcadores Ambientais , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Heptanos/farmacocinética , Heptanol/farmacocinética , Humanos , Cetonas/farmacocinética , Masculino , Reprodutibilidade dos Testes , Extração em Fase Sólida , Urinálise , Adulto Jovem
19.
Physiol Meas ; 39(2): 025002, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29303486

RESUMO

OBJECTIVE: We investigated canine hearts during ischemia after aortic cross clamping (UI, n = 20) and after HTK-cardioplegia (HTK, n = 24) at 35 °C, 25 °C, 15 °C, and 5 °C with the aim to compare tissue changes caused by the activity of anaerobic metabolism(AAM), cell membrane destruction(CD), and gap junction uncoupling(GJU). APPROACH: We measured continuously the complex dielectric spectrum(DS), ATP- and lactate content, extracellular pH, and rigor contracture. To identify changes in DS caused by AAM, CD, and GJU we performed additional experiments on the gap junction-free skeletal muscle. We used heart model simulations to calculate the effect of temperature. MAIN RESULTS: AAM affected the DS at 10 MHz and we found a strong correlation between DS and the proton concentration with a maximum of DS at 10 mmol g-1 dry weight in ATP-concentration. The time of GJU was detected by a characteristic increase in DS and CD by a characteristic decrease at 13 kHz. In comparison to UI, GJU, AAM and CD were delayed by HTK and by hypothermia, indicating a minimization of energy consumption and an improved preservation of tissue structure. SIGNIFICANCE: The novel findings were that in UI at 5 °C GJU occurred earlier and AAM remained constant, indicating a less effective preservation in UI by deep hypothermia in contrast to HTK.


Assuntos
Espectroscopia Dielétrica , Coração/efeitos dos fármacos , Isquemia/metabolismo , Isquemia/patologia , Trifosfato de Adenosina/metabolismo , Animais , Cães , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Glucose/farmacologia , Coração/fisiopatologia , Heptanol/farmacologia , Concentração de Íons de Hidrogênio , Hipotermia/complicações , Espaço Intracelular/metabolismo , Isquemia/complicações , Isquemia/fisiopatologia , Ácido Láctico/metabolismo , Manitol/farmacologia , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Temperatura
20.
J Mol Cell Cardiol ; 114: 150-160, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29097069

RESUMO

BACKGROUND: Chronic, excessive ethanol intake has been linked with various electrical instabilities, conduction disturbances, and even sudden cardiac death, but the underlying cause for the latter is insufficiently delineated. METHODS: We studied surface electrocardiography (ECG) in a community-dwelling cohort with moderate-to-heavy daily alcohol intake (grouped as >90g/day, ≤90g/day, and nonintake). RESULTS: Compared with nonintake, heavier alcohol users showed markedly widened QRS duration and higher prevalence of QRS fragmentation (64.3%, 50.9%, and 33.7%, respectively, χ2 12.0, both p<0.05) on surface ECG across the 3 groups. These findings were successfully recapitulated in 14-week-old C57BL/6 mice that were chronically given a 4% or 6% alcohol diet and showed dose-related slower action potential upstroke, reduced resting membrane potential, and disorganized or decreased intraventricular conduction (all p<0.05). Immunodetection further revealed increased ventricular collagen I depots with Cx43 downregulation and remodeling, together with clustered and diminished membrane Nav1.5 distribution. Administration of Cx43 blocker (heptanol) and Nav1.5 inhibitor (tetrodotoxin) in the mice each attenuated the suppression ventricular conduction compared with nonintake mice (p<0.05). CONCLUSIONS: Chronic excessive alcohol ingestion is associated with dose-related phenotypic intraventricular conduction disturbances and QRS fragmentation that can be recapitulated in mice. The mechanisms may involve suppressed gap junction and sodium channel functions, together with enhanced cardiac fibrosis that may contribute to arrhythmogenesis.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Conexina 43/metabolismo , Eletrocardiografia , Etanol/efeitos adversos , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/fisiopatologia , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Remodelação Ventricular , Potenciais de Ação/efeitos dos fármacos , Idoso , Animais , Feminino , Heptanol/farmacologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Tetrodotoxina/farmacologia
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