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https://www.readbyqxmd.com/read/28432761/protein-s-sulfhydration-by-hydrogen-sulfide-in-cardiovascular-system
#1
REVIEW
Guoliang Meng, Shuang Zhao, Liping Xie, Yi Han, Yong Ji
Hydrogen sulfide (H2 S), independent on any specific transporters, plays a number of biological effects on cardiovascular systems. However, the detailed mechanism of H2 S is not yet clear until now. Recently, a novel post-translational modification induced by H2 S, named S-sulfhydration, has been proposed. S-sulfhydration is a chemical modification on specific cysteine residues of target proteins by H2 S. There are several methods for S-sulfhydration detection, such as modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432653/analyzing-glycopeptide-isomers-by-combining-differential-mobility-spectrometry-with-electron-and-collision-based-tandem-mass-spectrometry
#2
J Larry Campbell, Takashi Baba, Chang Liu, Catherine S Lane, J C Yves Le Blanc, James W Hager
Differential mobility spectrometry (DMS) has been employed to separate isomeric species in several studies. Under the right conditions, factors such as separation voltage, temperature, the presence of chemical modifiers, and residence time can combine to provide unique signal channels for isomeric species. In this study, we examined a set of glycopeptide isomers, MUC5AC-3 and MUC5AC-13, which bear an N-acetyl-galactosamine (GalNAc) group on either threonine-3 or threonine-13. When analyzed as a mixture, the resulting MS and MS/MS spectra yield fragmentation patterns that cannot discern these convolved species...
April 21, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28432453/the-influence-of-oxo-bridged-binuclear-gold-iii-complexes-on-na-k-atpase-activity-a-joint-experimental-and-theoretical-approach
#3
Aleksandra M Bondžić, Mirjana B Čolović, Goran V Janjić, Božidarka Zarić, Sandra Petrović, Danijela Z Krstić, Tiziano Marzo, Luigi Messori, Vesna M Vasić
The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e., [(bipy2Me)2Au2(μ-O)2][PF6]2 (Auoxo6), Au2[(bipydmb-H)2(μ-O)][PF6] (Au2bipyC) and [Au2(phen(2Me))2(μ-O)2](PF6)2 (Au2phen) on Na/K-ATPase, purified from the porcine cerebral cortex, were investigated. All three studied gold complexes inhibited the enzyme activity in a concentration-dependent manner achieving IC50 values in the low micromolar range. Kinetic analysis suggested an uncompetitive mode of inhibition for Auoxo6 and Au2bipyC, and a mixed type one for Au2phen...
April 21, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28432359/role-of-the-ion-channel-extracellular-collar-in-ampa-receptor-gating
#4
Maria V Yelshanskaya, Samaneh Mesbahi-Vasey, Maria G Kurnikova, Alexander I Sobolevsky
AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#5
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28432032/neuronal-excitation-and-permeabilization-by-200-ns-pulsed-electric-field-an-optical-membrane-potential-study-with-fluovolt-dye
#6
Andrei G Pakhomov, Iurii Semenov, M Casciola, Shu Xiao
Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca(2+) signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431800/genetic-predictors-of-antipsychotic-response-to-lurasidone-identified-in-a-genome-wide-association-study-and-by-schizophrenia-risk-genes
#7
Jiang Li, Akane Yoshikawa, Mark D Brennan, Timothy L Ramsey, Herbert Y Meltzer
Biomarkers which predict response to atypical antipsychotic drugs (AAPDs) increases their benefit/risk ratio. We sought to identify common variants in genes which predict response to lurasidone, an AAPD, by associating genome-wide association study (GWAS) data and changes (Δ) in Positive And Negative Syndrome Scale (PANSS) scores from two 6-week randomized, placebo-controlled trials of lurasidone in schizophrenia (SCZ) patients. We also included SCZ risk SNPs identified by the Psychiatric Genomics Consortium using a polygenic risk analysis...
April 18, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28431535/ion-and-water-binding-sites-inside-an-occluded-hourglass-pore-of-a-trimeric-intracellular-cation-tric-channel
#8
Xiaomin Ou, Jianli Guo, Longfei Wang, Hanting Yang, Xiuying Liu, Jianyuan Sun, Zhenfeng Liu
BACKGROUND: Trimeric intracellular cation (TRIC) channels are crucial for Ca(2+) handling in eukaryotes and are involved in K(+) uptake in prokaryotes. Recent studies on the representative members of eukaryotic and prokaryotic TRIC channels demonstrated that they form homotrimeric units with the ion-conducting pores contained within each individual monomer. RESULTS: Here we report detailed insights into the ion- and water-binding sites inside the pore of a TRIC channel from Sulfolobus solfataricus (SsTRIC)...
April 22, 2017: BMC Biology
https://www.readbyqxmd.com/read/28430418/effects-of-small-polar-molecules-ma-and-h2o-on-degradation-processes-of-perovskite-solar-cells
#9
Chunqing Ma, Dong Shen, Jian Qing, Hrisheekesh Thachoth Chandran, Ming-Fai Lo, Chun-Sing Lee
Degradation mechanisms of methylammonium lead halide perovskite solar cells (PSCs) have drawn much attention recently. Herein, the bulk and surface degradation processes of the perovskite were differentiated for the first time by employing combinational studies using electrochemical impedance spectroscopy (EIS), capacitance frequency (CF), and X-ray diffraction (XRD) studies with particular attention on the roles of small polar molecules (MA(+) and H2O). CF study shows that short-circuit current density of the PSCs is increased by H2O at the beginning of the degradation process coupled with an increased surface capacitance...
April 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#10
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28430192/a-monodisperse-transmembrane-%C3%AE-helical-peptide-barrel
#11
Kozhinjampara R Mahendran, Ai Niitsu, Lingbing Kong, Andrew R Thomson, Richard B Sessions, Derek N Woolfson, Hagan Bayley
The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28429370/the-role-of-charged-residues-in-independent-glycine-receptor-folding-domains-for-intermolecular-interactions-and-ion-channel-function
#12
Georg Langlhofer, Carmen Villmann
Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4, and C-terminal sequences is essential for pentameric receptor arrangements. In vitro coexpressions of GlyRα1 truncated N-domains and C- domains were able to restore ion channel function. An ionic interaction between both domains was hypothesised as the underlying mechanism...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429325/gravitaxis-in-euglena
#13
Donat-P Häder, Ruth Hemmersbach
Motile microorganisms utilize a number of responses to external stimuli including light, temperature, chemicals as well as magnetic and electric fields. Gravity is a major clue to select a niche in their environment. Positive gravitaxis leads an organism down into the water column and negative gravitaxis brings it to the surface. In Euglena the precision of gravitaxis is regulated by an internal rhythm entrained by the daily light/dark cycle. This and the cooperation with phototaxis bring the cells into an optimal position in the water column...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28429004/binding-site-opening-by-loop-c-shift-and-chloride-ion-pore-interaction-in-the-gabaa-receptor-model
#14
M A Michałowski, S Kraszewski, J W Mozrzymas
GABAA receptors (GABAARs) are crucial in mediating inhibition in the adult mammalian brain. Although the kinetics of this receptor has been extensively studied, the molecular picture of interactions occurring at various channel conformations remains elusive. While electrophysiology combined with mutagenesis sheds light on the role of specific residues, ultrastructural studies reveal static structures which, in the case of GABAARs, are limited to the β3 homomer. To take advantage of the newest crystal structures of cys-loop receptors, a homology model of α1β2γ2 GABAAR in the unbound closed state was built using a template of the homomeric glycine receptor in the closed state...
April 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28428744/mutational-analysis-at-intersubunit-interfaces-of-an-anionic-glutamate-receptor-reveals-a-key-interaction-important-for-channel-gating-by-ivermectin
#15
Nurit Degani-Katzav, Revital Gortler, Marina Weissman, Yoav Paas
The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an open-channel conformation of invertebrate chloride-selective glutamate receptors (GluClRs), thereby causing a continuous inflow of chloride ions and sustained membrane hyperpolarization. These effects suppress nervous impulses and vital physiological processes in parasitic nematodes. The GluClRs are pentamers. Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans) GluClα (GLC-1) subunit can inherently respond to IVM but not to glutamate (the neurotransmitter)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28428630/hinge-deleted-igg4-blocker-therapy-for-acetylcholine-receptor-myasthenia-gravis-in-rhesus-monkeys
#16
Mario Losen, Aran F Labrijn, Vivianne H van Kranen-Mastenbroek, Maarten L Janmaat, Krista G Haanstra, Frank J Beurskens, Tom Vink, Margreet Jonker, Bert A 't Hart, Marina Mané-Damas, Peter C Molenaar, Pilar Martinez-Martinez, Eline van der Esch, Janine Schuurman, Marc H de Baets, Paul W H I Parren
Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428547/the-tarantula-toxin-%C3%AE-%C3%AE-trtx-pre1a-highlights-the-importance-of-the-s1-s2-voltage-sensor-region-for-sodium-channel-subtype-selectivity
#17
Joshua S Wingerd, Christine A Mozar, Christine A Ussing, Swetha S Murali, Yanni K-Y Chin, Ben Cristofori-Armstrong, Thomas Durek, John Gilchrist, Christopher W Vaughan, Frank Bosmans, David J Adams, Richard J Lewis, Paul F Alewood, Mehdi Mobli, Macdonald J Christie, Lachlan D Rash
Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428534/expression-of-acid-sensing-ion-channels-in-renal-tubular-epithelial-cells-and-their-role-in-patients-with-henoch-sch%C3%A3-nlein-purpura-nephritis
#18
Li-Ping Yuan, Yan Bo, Zhang Qin, Hua Ran, Wang Li, Yu-Fei Li, Gui Ming
BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis...
April 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28428226/rapid-throughput-analysis-of-gabaa-receptor-subtype-modulators-and-blockers-using-disbac1-3-membrane-potential-red-dye
#19
Atefeh Mousavi Nik, Brandon Pressly, Vikrant Singh, Shane Antrobus, Susan Hulsizer, Michael A Rogawski, Heike Wulff, Isaac N Pessah
Fluorometric Imaging Plate Reader (FLIPR®) membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high throughput drug screening for G-protein coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABAA receptor (GABAAR) isoforms (synaptic α1β3γ2, extrasynaptic α4β3δ, and β3 homopentomers). High-resolution mass spectrometry identified FMP-Red-dye as DisSBAC1(3). GABAAR expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane (Em) potentials compared to GABAAR-null cells...
April 20, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28428202/precision-physiology-and-rescue-of-brain-ion-channel-disorders
#20
REVIEW
Jeffrey Noebels
Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution...
April 20, 2017: Journal of General Physiology
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