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https://www.readbyqxmd.com/read/28539652/ano1-inhibits-cardiac-fibrosis-after-myocardial-infraction-via-tgf-%C3%AE-smad3-pathway
#1
Yao Gao, Yan Mei Zhang, Li Jun Qian, Ming Chu, Jian Hong, Di Xu
As a newly identified factor in calcium-activated chloride channel, ANO1 participates in various physiological processes like proliferation and differentiation, and expresses in human cardiac fibroblasts. In this experiment, we investigated the function of ANO1 in cardiac fibrosis after myocardial infraction (MI) with methods of Western blotting, Quantitative real-time PCR (qRT-PCR), metabolic reduction of 3-(4,5-dimethylthiozol-2-yl)-2, 5-diphenyltetrazo-lium bromide (MTT), immunofluorescence and confocal imaging, and Masson's trichrome staining...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536821/impaired-motor-coordination-and-learning-in-mice-lacking-anoctamin-2-calcium-gated-chloride-channels
#2
Franziska Neureither, Katharina Ziegler, Claudia Pitzer, Stephan Frings, Frank Möhrlen
Neurons communicate through excitatory and inhibitory synapses. Both lines of communication are adjustable and allow the fine tuning of signal exchange required for learning processes in neural networks. Several distinct modes of plasticity modulate glutamatergic and GABAergic synapses in Purkinje cells of the cerebellar cortex to promote motor control and learning. In the present paper, we present evidence for a role of short-term ionic plasticity in the cerebellar circuit activity. This type of plasticity results from altered chloride driving forces at the synapses that molecular layer interneurons form on Purkinje cell dendrites...
May 23, 2017: Cerebellum
https://www.readbyqxmd.com/read/28536536/rna-seq-comparison-of-larval-and-adult-malpighian-tubules-of-the-yellow-fever-mosquito-aedes-aegypti-reveals-life-stage-specific-changes-in-renal-function
#3
Yiyi Li, Peter M Piermarini, Carlos J Esquivel, Hannah E Drumm, Faye D Schilkey, Immo A Hansen
Introduction: The life history of Aedes aegypti presents diverse challenges to its diuretic system. During the larval and pupal life stages mosquitoes are aquatic. With the emergence of the adult they become terrestrial. This shifts the organism within minutes from an aquatic environment to a terrestrial environment where dehydration has to be avoided. In addition, female mosquitoes take large blood meals, which present an entirely new set of challenges to salt and water homeostasis. Methods: To determine differences in gene expression associated with these different life stages, we performed an RNA-seq analysis of the main diuretic tissue in A...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28536248/the-signaling-lipid-phosphatidylinositol-3-5-bisphosphate-targets-plant-clc-a-anion-h-exchange-activity
#4
Armando Carpaneto, Anna Boccaccio, Laura Lagostena, Eleonora Di Zanni, Joachim Scholz-Starke
Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) is a low-abundance signaling lipid associated with endo-lysosomal and vacuolar membranes in eukaryotic cells. Recent studies on Arabidopsis indicated a critical role of PI(3,5)P2 in vacuolar acidification and morphology during ABA-induced stomatal closure, but the molecular targets in plant cells remained unknown. By using patch-clamp recordings on Arabidopsis vacuoles, we show here that PI(3,5)P2 does not affect the activity of vacuolar H(+)-pyrophosphatase or vacuolar H(+)-ATPase...
May 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28534947/research-and-progress-on-clc%C3%A2-2-review
#5
Hongwei Wang, Minghui Xu, Qingjie Kong, Peng Sun, Fengyun Yan, Wenying Tian, Xin Wang
Chloride channel 2 (ClC-2) is one of the nine mammalian members of the ClC family. The present review discusses the molecular properties of ClC‑2, including CLCN2, ClC‑2 promoter and the structural properties of ClC‑2 protein; physiological properties; functional properties, including the regulation of cell volume. The effects of ClC‑2 on the digestive, respiratory, circulatory, nervous and optical systems are also discussed, in addition to the mechanisms involved in the regulation of ClC‑2. The review then discusses the diseases associated with ClC‑2, including degeneration of the retina, Sjögren's syndrome, age‑related cataracts, degeneration of the testes, azoospermia, lung cancer, constipation, repair of impaired intestinal mucosa barrier, leukemia, cystic fibrosis, leukoencephalopathy, epilepsy and diabetes mellitus...
May 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534100/dose-dependent-differential-effects-of-in-vivo-exposure-of-cadmium-on-myometrial-activity-in-rats-involvement-of-vdcc-and-ca-2-mimicking-pathways
#6
Vivek K Saroj, Udayraj P Nakade, Abhishek Sharma, Soumen Choudhury, Sunil W Hajare, Satish K Garg
Present study was undertaken to study the effect of 28-days exposure of female adult rats to cadmium (Cd) in drinking water @ 3, 10 and 30 parts per million (ppm) on myometrial responsiveness to different spasmogens and unravel the possible mechanism of alterations in myometrial activity. Cadmium and Ca(2+) levels in blood and uterus were measured by atomic absorption spectroscopy while isometric tension in myometrial strips was measured using data acquisition system-based physiograph. Dose-dependent increase in levels of cadmium was observed in both blood and uterus while calcium was increased only in the uterus as compared to those in control...
May 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28533270/classical-activation-of-macrophages-and-vardenafil
#7
Richmond Muimo
Inhibitors of phosphodiesterase 5 (PDE5) - sildenafil citrate (Viagra; Pfizer) and vardenafil hydrochloride (Levitra; Bayer/GlaxoSmithKline) - approved for the treatment of erectile dysfunction and pulmonary arterial hypertension also rescue the loss of cystic fibrosis (CF) chloride channel function and the mislocalization of F508del-CFTR in affected tissues in CF. Can PDE5 inhibitors provide a therapeutic strategy which combines ability to correct the basic ion transport defect and to control de-regulated lung inflammation in CF?...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28530296/post-cycloaddition-modification-of-a-porous-mof-for-improved-gc-separation-of-ethanol-and-water
#8
Ya-Jun Zhang, Cheng Chen, Li-Xuan Cai, Bin Tan, Xiao-Dong Yang, Jie Zhang, Min Ji
An olefin-containing pyridinium derivative, 1-(4-carboxybenzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium chloride (HBCbpeCl) has been introduced into a novel 2D metal-organic framework with rare right- and left-handed spiral nanotubular channels arranged alternately in the structure. The 1D channel is modified by positively-charged pyridinium segments, which shows high affinities to Lewis basic molecules such as methanol, ethanol, and water vapor. Additionally, the BCbpe molecules in the structure have been directed through cation-π interactions to be aligned antiparallel to each other with the C[double bond, length as m-dash]C double bond arranged properly for [2 + 2] photocycloaddition, which can be triggered to undergo structural transformation from 2D to 3D...
May 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28528670/glycine-receptor-drug-discovery
#9
Joseph W Lynch, Yan Zhang, Sahil Talwar, Argel Estrada-Mondragon
Postsynaptic glycine receptor (GlyR) chloride channels mediate inhibitory neurotransmission in the spinal cord and brain stem, although presynaptic and extrasynaptic GlyRs are expressed more widely throughout the brain. In humans, GlyRs are assembled as homo- or heteromeric pentamers of α1-3 and β subunits. GlyR malfunctions have been linked to a range of neurological disorders including hyperekplexia, temporal lobe epilepsy, autism, breathing disorders, and chronic inflammatory pain. Although it is possible that GlyRs may eventually be clinically targeted for a variety of neurological disorders, most research to date has focused on developing GlyR-targeted treatments for chronic pain...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#10
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28504490/additive-effect-of-mesenchymal-stem-cells-and-defibrotide-in-an-arterial-rat-thrombosis-model
#11
Dilek Dilli, Emine Kılıç, Nihat Yumuşak, Serdar Beken, Duygu Uçkan Çetinkaya, Ramazan Karabulut, Ayşegu L Zenciroğlu
BACKGROUND/AIM: In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. METHODS: Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT...
June 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28496181/the-neuronal-k-cl-co-transporter-2-slc12a5-modulates-insulin-secretion
#12
Shams Kursan, Timothy S McMillen, Pavani Beesetty, Eduardo Dias-Junior, Mohammed M Almutairi, Abu A Sajib, J Ashot Kozak, Lydia Aguilar-Bryan, Mauricio Di Fulvio
Intracellular chloride concentration ([Cl(-)]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl(-) loaders such as the Na(+)K(+)2Cl(-) co-transporter 1 (Slc12a2) over Cl(-)extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" K(+)Cl(-) co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28493701/substituted-2-acylamino-cycloalkylthiophene-3-carboxylic-acid-arylamides-as-inhibitors-of-the-calcium-activated-chloride-channel-transmembrane-protein-16a-tmem16a
#13
Eric C Truong, Puay-Wah Phuan, Amanda L Reggi, Loretta Ferrera, Luis J V Galietta, Sarah E Levy, Alannah C Moises, Onur Cil, Elena Diez-Cecilia, Sujin Lee, Alan S Verkman, Marc O Anderson
Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report by screening the discovery of 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A, and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa)...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28483640/characterization-of-constitutive-and-acid-induced-outwardly-rectifying-chloride-currents-in-immortalized-mouse-distal-tubular-cells
#14
William C Valinsky, Rhian M Touyz, Alvin Shrier
Thiazides block Na(+) reabsorption while enhancing Ca(2+) reabsorption in the kidney. As previously demonstrated in immortalized mouse DCT (MDCT) cells, chlorothiazide application induced a robust plasma membrane hyperpolarization, which increased Ca(2+) uptake. This essential thiazide-induced hyperpolarization was prevented by the Cl(-) channel inhibitor 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), implicating NPPB-sensitive Cl(-) channels, however the nature of these Cl(-) channels has been rarely described in the literature...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28479061/crystal-structures-of-human-glyr%C3%AE-3-bound-to-ivermectin
#15
Xin Huang, Hao Chen, Paul L Shaffer
Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRα1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive...
May 4, 2017: Structure
https://www.readbyqxmd.com/read/28470528/phenotyping-cellular-viability-by-functional-analysis-of-ion-channels-glyr-targeted-screening-in-nt2-n-cells
#16
Katharina Kuenzel, Sepideh Abolpour Mofrad, Daniel F Gilbert
Glycine receptor chloride channels (GlyRs) are attractive drug targets for therapeutic intervention and are also more and more recognized in the context of in vitro neurotoxicity and developmental neurotoxicity testing. Assaying the functional properties of GlyR can serve as an indicator of cellular viability and the integrity of the developing and mature central nervous system. Human pluripotent NTERA-2 (NT2) stem cells undergo neuronal differentiation upon stimulation with retinoic acid and express a large variety of neuronal proteins-including GlyR...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28469061/synthesis-structural-characterization-and-computational-studies-of-catena-poly-chlorido-%C3%AE-3-pyridin-1-ium-3-yl-phosphonato-%C3%AE%C2%BA-3-o-o-o-zinc-ii
#17
Magdalena Wilk-Kozubek, Katarzyna N Jarzembska, Jan Janczak, Veneta Videnova-Adrabinska
Coordination polymers are constructed from two basic components, namely metal ions, or metal-ion clusters, and bridging organic ligands. Their structures may also contain other auxiliary components, such as blocking ligands, counter-ions and nonbonding guest or template molecules. The choice or design of a suitable linker is essential. The new title zinc(II) coordination polymer, [Zn(C5H5NO3P)Cl]n, has been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction and vibrational spectroscopy (FT-IR and FT-Raman)...
May 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/28468943/estradiol-activates-chloride-channels-via-the-estrogen-receptor-alpha-in-the-cell-membrane-in-osteoblasts
#18
Zhiqin Deng, Shuang Peng, Yanfang Zheng, Xiaoya Yang, Haifeng Zhang, Qiuchan Tan, Xiechou Liang, Hong Gao, Yuan Li, Yanqing Huang, Linyan Zhu, Tim Jc Jacob, Lixin Chen, Liwei Wang
Estrogen plays important roles in regulation of bone formation. Chloride channels in the ClC family are expressed in osteoblasts and are associated with bone physiology and pathology, but the relationship between chloride channels and estrogen is not clear. In this study, the action of estrogen on chloride channels was investigated in osteoblastic MC3T3-E1 cells. Results showed that 17β-estradiol could activate a current which reversed at a potential close to Cl(-) equilibrium potential with the anion selectivity I- >Br->Cl->gluconate and was inhibited by the chloride channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and knockdown of ClC-3 chloride channel expression...
May 3, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28465373/mashiningan-improves-opioid-induced-constipation-in-rats-by-activating-cystic-fibrosis-transmembrane-conductance-regulator-chloride-channel
#19
Yumi Harada, Seiichi Iizuka, Yayoi Saegusa, Sachiko Mogami, Naoki Fujitsuka, Tomohisa Hattori
Opioid receptor stimulants are analgesics used in patients with and without cancer; however, they often cause constipation, resulting in poor adherence and deterioration of the quality of life. Hence, suitable treatments for constipation are required. In this study, we investigated the pharmacological mechanisms of action of mashiningan (MNG), a Kampo medicine used to treat constipation, and evaluated the effect of MNG on opioid-induced constipation in rats. MNG (100 or 300 mg/kg) was orally administered to normal or codeine phosphate (CPH)-induced constipation in rats, and its effect was evaluated on the basis of fecal counts, characteristics, and weight...
May 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28463591/rab-gtpases-regulate-the-trafficking-of-channels-and-transporters-a-focus-on-cystic-fibrosis
#20
Carlos M Farinha, Paulo Matos
The amount of ion channels and transporters present at the plasma membrane is a crucial component of the overall regulation of ion transport. The number of channels present result from an intricate network of proteins that controls the late events of channel trafficking, such as endocytosis, recycling and targeting to lysosomal degradation. Small GTPases of the Rab family are key players in these processes thus contributing to regulation of fluid secretion and ion homeostasis. In epithelia, this involves mainly the balance between the chloride channel CFTR and the sodium channel ENaC, whose misfunction is a hallmark of cystic fibrosis - the commonest recessive disorder in Caucasians...
May 2, 2017: Small GTPases
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