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https://www.readbyqxmd.com/read/29474201/mechanical-ventilation-induces-desensitization-of-lung-axl-tyrosine-kinase-receptors
#1
Gail Otulakowski, Doreen Engelberts, Martin Post, Claire Masterson, Brian P Kavanagh
BACKGROUND: Lower tidal volumes are increasingly used in acute respiratory distress syndrome, but mortality has changed little in the last 20 yr. Therefore, in addition to ventilator settings, it is important to target molecular mediators of injury. Sepsis and other inflammatory states increase circulating concentrations of Gas6, a ligand for the antiinflammatory receptor Axl, and of a soluble decoy form of Axl. We investigated the effects of lung stretch on Axl signaling. METHODS: We used a mouse model of early injury from high tidal volume and assessed the effects of inhibiting Axl on in vivo lung injury (using an antagonist R428, n = 4/group)...
February 23, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29471754/anoctamin-channels-in-human-myometrium-a-novel-target-for-tocolysis
#2
Jennifer Danielsson, Joy Vink, Shunsuke Hyuga, Xiao Wen Fu, Hiromi Funayama, Ronald Wapner, Andrew M Blanks, George Gallos
BACKGROUND: Spontaneous preterm labor leading to preterm birth is a significant obstetric problem leading to neonatal morbidity and mortality. Current tocolytics are not completely effective and novel targets may afford a therapeutic benefit. OBJECTIVE: To determine whether the anoctamin (ANO) family, including the calcium-activated chloride channel ANO1, is present in pregnant human uterine smooth muscle (USM) and whether pharmacological and genetic modulation of ANO1 modulates USM contraction...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29467616/molecular-characterization-of-gaba-a-receptor-subunit-diversity-within-major-peripheral-organs-and-their-plasticity-in-response-to-early-life-psychosocial-stress
#3
Ethan A Everington, Adina G Gibbard, Jerome D Swinny, Mohsen Seifi
Gamma aminobutyric acid (GABA) subtype A receptors (GABAA Rs) are integral membrane ion channels composed of five individual proteins or subunits. Up to 19 different GABAA R subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3) have been identified, resulting in anatomically, physiologically, and pharmacologically distinct multiple receptor subtypes, and therefore GABA-mediated inhibition, across the central nervous system (CNS). Additionally, GABAA R-modulating drugs are important tools in clinical medicine, although their use is limited by adverse effects...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29463274/along-with-its-favorable-prognostic-role-clca2-inhibits-growth-and-metastasis-of-nasopharyngeal-carcinoma-cells-via-inhibition-of-fak-erk-signaling
#4
Yuan-Yuan Qiang, Chang-Zhi Li, Rui Sun, Li-Sheng Zheng, Li-Xia Peng, Jun-Ping Yang, Dong-Fang Meng, Yan-Hong Lang, Yan Mei, Ping Xie, Liang Xu, Yun Cao, Wen-Wen Wei, Li Cao, Hao Hu, Qin Yang, Dong-Hua Luo, Ying-Ying Liang, Bi-Jun Huang, Chao-Nan Qian
BACKGROUND: CLCA2 was reported as a tumor suppressor and disregulated in breast cancer. However, its function in tumor growth and metastasis in NPC has rarely been reported. In this study, we investigated the functional and molecular mechanisms by which CLCA2 influences NPC. METHODS: CLCA2 expression in human NPC cell lines and tissues was examined via real-time PCR (RT-PCR), Western blot and IHC. The biological roles of CLCA2 in proliferative, migration and invasion of NPC cell lines was evaluated in 5-8F, S18, S26 and SUNE-1 cells...
February 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29462791/the-cellular-chloride-channels-clic1-and-clic4-contribute-to-virus-mediated-cell-motility
#5
Gabrielė Stakaitytė, Nnenna Nwogu, Jonathan D Lippiat, G Eric Blair, Krzysztof Poterlowicz, James R Boyne, Andrew Macdonald, Jamel Mankouri, Adrian Whitehouse
Ion channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K+ and Cl- channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily due to the expression of two early regulatory proteins termed small and large tumour antigens (ST and LT, respectively)...
February 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29460030/succinic-semialdehyde-dehydrogenase-deficiency-a-disorder-of-gaba-metabolism-an-update-on-pharmacological-and-enzyme-replacement-therapeutic-strategies
#6
Kara R Vogel, Garrett R Ainslie, Dana C Walters, Alice McConnell, Sameer C Dhamne, Alexander Rotenberg, Jean-Baptiste Roullet, K Michael Gibson
We present an update to the status of research on succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD), a rare disorder of GABA metabolism. This is an unusual disorder featuring the accumulation of both GABA and its neuromodulatory analog, gamma-hydroxybutyric acid (GHB), and recent studies have advanced the potential clinical application of NCS-382, a putative GHB receptor antagonist. Animal studies have provided proof-of-concept that enzyme replacement therapy could represent a long-term therapeutic option...
February 19, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29453758/theoretical-study-on-the-optical-response-behavior-to-hydrogen-chloride-gas-of-a-series-of-schiff-base-based-star-shaped-structures
#7
Fei Wang, Tianhong Qi, Zhongmin Su, Yuzhong Xie
Schiff-base compounds have many applications in the field of optoelectronic materials and chemical sensing because of their appealing coordination ability, and simple and easily accessible use in structural modification. Herein, five kinds of star-shaped Schiff-base compounds were designed and their optical response behavior to hydrogen chloride (HCl) gas was studied using dependent/time-dependent density functional theory (DFT/TDDFT). Moreover, the relationship between structures and properties was investigated upon changing the benzene group into N atom or triazine group at the core-position and introducing a methoxyl (-OCH 3 ) or nitro (-NO 2 ) group into the star-shaped Schiff-bases at the tail of the branches...
February 17, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29449621/polygonum-aviculare-l-extract-and-quercetin-attenuate-contraction-in-airway-smooth-muscle
#8
Xi Luo, Lu Xue, Hao Xu, Qing-Yang Zhao, Qian Wang, Yu-Shan She, Dun-An Zang, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Meng-Fei Yu, Weiwei Chen, Li-Qun Ma, Shu Chen, Shanshan Chen, Xiangning Fu, Sheng Hu, Xiaowei Nie, Chenyou Shen, Chunbin Zou, Gangjian Qin, Jiapei Dai, Guangju Ji, Yunchao Su, Shen Hu, Jingyu Chen, Qing-Hua Liu
Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+ -induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29448982/stochastic-gating-as-a-novel-mechanism-for-channel-selectivity
#9
Alexander M Berezhkovskii, Sergey M Bezrukov
An ideal channel, responsible for metabolite fluxes in and out of the cells and cellular compartments, is supposed to be selective for a particular set of molecules only. However, such a channel has to be wide enough to accommodate relatively large metabolites, and, therefore, it allows passage of smaller solutes, for example, sodium, potassium, and chloride ions, thus compromising membrane's barrier function. Here we show that stochastic gating is able to provide a mechanism for the selectivity of wide channels in favor of large metabolites...
February 12, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29446321/pulmonary-il-1%C3%AE-expression-in-early-life-causes-permanent-changes-in-lung-structure-and-function-in-adulthood
#10
Anna Hogmalm, Maija Bry, Kristina Bry
Chorioamnionitis, mechanical ventilation, oxygen therapy, and postnatal infection promote inflammation in the newborn lung. The long-term consequences of pulmonary inflammation during infancy have not been well characterized. The aim of this study was to examine the impact of inflammation during the late saccular to alveolar stages of lung development on lung structure and function in adulthood. To induce IL-1β expression in the pulmonary epithelium of mice with a tetracycline-inducible human IL-1β transgene, doxycycline was administered via intraperitoneal injections to bitransgenic pups and their littermate controls on postnatal days (PN) 0, 0...
February 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29444316/glucose-triggers-stomatal-closure-mediated-by-gin1-gin2-pyr-rcar-ros-no-cdpk6-and-slac1-in-arabidposis
#11
Yan Li, Shanshan Xu, Zhiwei Wang, Lingchao He, Kang Xu, Genxuan Wang
Sugars play important roles in regulating plant growth, development and stomatal movement. Here, we found that glucose triggered stomatal closure, showing a dose-and time-dependent manner in Arabidopsis. Pharmacological data showed that glucose-induced stomatal closure was greatly inhibited by catalase (CAT, a reactive oxygen species (ROS) scavenger), diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor), lanthanum chloride (LaCl3, a Ca2+ channel blocker), ethylene glycol tetraacetic acid (EGTA, a Ca2+ chelator), two nitrate reductase (NR) inhibitors, tungstate and sodium azide (NaN3), while not affected by salicylhydroxamic acid (SHAM, a peroxidase inhibitor)...
February 10, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29442545/novel-compound-heterozygous-clcnkb-gene-mutations-c-1755a-g-c-848_850deltct-cause-classic-bartter-syndrome
#12
Chunli Wang, Ying Chen, Bixia Zheng, Mengshu Zhu, Jia Fan, Juejin Wang, Zhanjun Jia, Songming Huang, Aihua Zhang
Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother...
February 14, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29439248/transient-receptor-potential-vanilloid-4-activation-induced-increase-in-glycine-activated-current-in-mouse-hippocampal-pyramidal-neurons
#13
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29436285/m%C3%A3-ni%C3%A3-re-s-disease-pathophysiology-endolymphatic-sac-immunohistochemical-study-of-aquaporin-2-v2r-vasopressin-receptor-nkcc2-and-trpv4
#14
Marc-Henri Asmar, Louis Gaboury, Issam Saliba
Objectives Endolymphatic sac (ELS) pathophysiology in Ménière's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin-2 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops...
February 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29430647/the-cells-and-conductance-mediating-cholinergic-neurotransmission-in-the-murine-proximal-stomach
#15
Tae Sik Sung, Sung Jin Hwang, Sang Don Koh, Yulia Bayguinov, Lauen E Peri, Peter J Blair, Timothy I Webb, David M Pardo, Jason R Rock, Kenton M Sanders, Sean M Ward
Enteric motor neurotransmission is essential for normal gastrointestinal (GI) motility. Controversy exists regarding the cells and ionic conductance(s) that mediate post-junctional neuroeffector responses to motor neurotransmitters. Isolated intramuscular ICC (ICC-IM) and smooth muscle cells (SMCs) from murine fundus muscles were used to determine the conductances activated by carbachol (CCh) in each cell-type. The calcium-activated chloride conductance (CaCC), Ano1 is expressed by ICC-IM but not resolved in SMCs, and CCh activated a Cl- conductance in ICC-IM and a non-selective cation conductance (NSCC) in SMCs...
February 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29427588/hyperpolarization-by-n-3-oxododecanoyl-l-homoserine-lactone-a-quorum-sensing-molecule-in-rat-thymic-lymphocytes
#16
Yumiko Nishimura-Danjobara, Keisuke Oyama, Kumio Yokoigawa, Yasuo Oyama
To study the adverse effects of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum sensing molecule, on mammalian host cells, its effect on membrane potential was examined in rat thymic lymphocytes using flow cytometric techniques with a voltage-sensitive fluorescent probe. As 3-300 μM ODHL elicited hyperpolarization, it is likely that it increases membrane K+ permeability because hyperpolarization is directly linked to changing K+ gradient across membranes, but not Na+ and Cl- gradients. ODHL did not increase intracellular Ca2+ concentration...
February 7, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29425673/structural-stability-of-purified-human-cftr-is-systematically-improved-by-mutations-in-nucleotide-binding-domain-1
#17
Zhengrong Yang, Ellen Hildebrandt, Fan Jiang, Andrei A Aleksandrov, Netaly Khazanov, Qingxian Zhou, Jianli An, Andrew T Mezzell, Bala M Xavier, Haitao Ding, John R Riordan, Hanoch Senderowitz, John C Kappes, Christie G Brouillette, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is an ABC transporter containing two transmembrane domains forming a chloride ion channel, and two nucleotide binding domains (NBD1 and NBD2). CFTR has presented a formidable challenge to obtain monodisperse, biophysically stable protein. Here we report a comprehensive study comparing effects of single and multiple NBD1 mutations on stability of both the NBD1 domain alone and on purified full length human CFTR. Single mutations S492P, A534P, I539T acted additively, and when combined with M470V, S495P, and R555K cumulatively yielded an NBD1 with highly improved structural stability...
February 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29422883/detecting-cortical-spreading-depolarization-with-full-band-scalp-electroencephalography-an-illusion
#18
Jeannette Hofmeijer, C R van Kaam, Babette van de Werff, Sarah E Vermeer, Marleen C Tjepkema-Cloostermans, Michel J A M van Putten
Introduction: There is strong evidence suggesting detrimental effects of cortical spreading depolarization (CSD) in patients with acute ischemic stroke and severe traumatic brain injury. Previous studies implicated scalp electroencephalography (EEG) features to be correlates of CSD based on retrospective analysis of EEG epochs after having detected "CSD" in time aligned electrocorticography. We studied the feasibility of CSD detection in a prospective cohort study with continuous EEG in 18 patients with acute ischemic stroke and 18 with acute severe traumatic brain injury...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29422673/small-molecule-anionophores-promote-transmembrane-anion-permeation-matching-cftr-activity
#19
Elsa Hernando, Valeria Capurro, Claudia Cossu, Michele Fiore, María García-Valverde, Vanessa Soto-Cerrato, Ricardo Pérez-Tomás, Oscar Moran, Olga Zegarra-Moran, Roberto Quesada
Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29421809/a-potassium-selective-current-affected-by-micromolar-concentrations-of-anion-transport-inhibitors
#20
Roberta Costa, Davide Antonio Civello, Emanuele Bernardinelli, Simone Vanoni, Michaela Zopf, Giada Scantamburlo, Charity Nofziger, Wolfgang Patsch, Markus Paulmichl, Silvia Dossena
BACKGROUND/AIMS: In the human genome, more than 400 genes encode ion channels, which are ubiquitously expressed and often coexist and participate in almost all physiological processes. Therefore, ion channel blockers represent fundamental tools in discriminating the contribution of individual channel types to a physiological phenomenon. However, unspecific effects of these compounds may represent a confounding factor. Three commonly used chloride channel inhibitors, i.e. 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS), 5-nitro-2-[(3-phenylpropyl) amino]benzoic acid (NPPB) and the anti-inflammatory drug niflumic acid were tested to identify the lowest concentration effective on Cl- channels and ineffective on K+ channels...
February 2, 2018: Cellular Physiology and Biochemistry
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