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https://www.readbyqxmd.com/read/29236691/activation-mechanism-of-the-calcium-activated-chloride-channel-tmem16a-revealed-by-cryo-em
#1
Cristina Paulino, Valeria Kalienkova, Andy K M Lam, Yvonne Neldner, Raimund Dutzler
The calcium-activated chloride channel TMEM16A is a ligand-gated anion channel that opens in response to an increase in intracellular Ca2+ concentration. The protein is broadly expressed and contributes to diverse physiological processes, including transepithelial chloride transport and the control of electrical signalling in smooth muscles and certain neurons. As a member of the TMEM16 (or anoctamin) family of membrane proteins, TMEM16A is closely related to paralogues that function as scramblases, which facilitate the bidirectional movement of lipids across membranes...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29236684/cryo-em-structures-of-the-tmem16a-calcium-activated-chloride-channel
#2
Shangyu Dang, Shengjie Feng, Jason Tien, Christian J Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi, Tingxu Chen, Charles S Craik, Yuh Nung Jan, Daniel L Minor, Yifan Cheng, Lily Yeh Jan
Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29235532/investigation-of-the-effects-of-the-cftr-potentiator-ivacaftor-on-human-p-glycoprotein-abcb1
#3
Swathi Lingam, Nopnithi Thonghin, Robert C Ford
Ivacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use for the chronic treatment of cystic fibrosis in patients. There is evidence that the bioavailability of ivacaftor in the body may be influenced by the multi-drug exporter P-glycoprotein. Here we have employed purified and reconstituted P-glycoprotein to study its interaction with ivacaftor as well as the ability of the drug to compete with a known transported substrate of the protein. We find that ivacaftor stimulates the ATPase activity of the purified protein and can compete with the transport of the fluorescent substrate Hoechst 33342...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29231977/dids-inhibits-overexpression-bak1-induced-mitochondrial-apoptosis-through-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway
#4
Xiayun Yang, Shusheng Tang, Daowen Li, Xiaohong Yu, Fuyun Wang, Xilong Xiao
Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29229864/cytoplasmic-cl-couples-membrane-remodeling-to-epithelial-morphogenesis
#5
Mu He, Wenlei Ye, Won-Jing Wang, Eirish S Sison, Yuh Nung Jan, Lily Yeh Jan
Chloride is the major free anion in the extracellular space (>100 mM) and within the cytoplasm in eukaryotes (10 ∼ 20 mM). Cytoplasmic Cl- level is dynamically regulated by Cl- channels and transporters. It is well established that movement of Cl- across the cell membrane is coupled with cell excitability through changes in membrane potential and with water secretion. However, whether cytoplasmic Cl- plays additional roles in animal development and tissue homeostasis is unknown. Here we use genetics, cell biological and pharmacological tools to demonstrate that TMEM16A, an evolutionarily conserved calcium-activated chloride channel (CaCC), regulates cytoplasmic Cl- homeostasis and promotes plasma membrane remodeling required for mammalian epithelial morphogenesis...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29211365/oral-cavity-health-among-cystic-fibrosis-patients-literature-overview
#6
REVIEW
Katarzyna Herman, Małgorzata Kowalczyk-Zając, Tomasz Pytrus
Cystic fibrosis is a genetic disorder in which the mutation of the Cystis Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes the protein forming a chloride channel of epithelial cells results in its distorted functioning. The manifestations of the disorder are mainly observed in the respiratory and digestive system. Accumulation of sticky and thick mucus is the dominant clinical symptom; it leads to chronic infections and gradual tissue destruction. Although cystic fibrosis remains incurable, it is currently feasible to extend patients' life expectancy thanks to modern therapy possibilities...
October 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29204713/gabaa-receptor-subtype-mechanisms-and-the-abuse-related-effects-of-ethanol-genetic-and-pharmacological-evidence
#7
Cassie M Chandler, John S Overton, Daniela Rüedi-Bettschen, Donna M Platt
Ethanol's reinforcing and subjective effects, as well as its ability to induce relapse, are powerful factors contributing to its widespread use and abuse. A significant mediator of these behavioral effects is the GABAA receptor system. GABAA receptors are the target for γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. Structurally, they are pentameric, transmembrane chloride ion channels comprised of subunits from at least eight different families of distinct proteins. The contribution of different GABAA subunits to ethanol's diverse abuse-related effects is not clear and remains an area of research focus...
December 5, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29200904/taurine-relaxes-human-radial-artery-through-potassium-channel-opening-action
#8
Kemal Gokhan Ulusoy, Erkan Kaya, Kubilay Karabacak, Melik Seyrek, İbrahim Duvan, Vedat Yildirim, Oguzhan Yildiz
The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29198705/tilapia-and-human-clic2-structures-are-highly-conserved
#9
Jiao Zeng, Zhengjun Li, Eei Yin Lui, Siew Hong Lam, Kunchithapadam Swaminathan
Chloride intracellular channels (CLICs) exist in soluble and membrane bound forms. We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. We have also compared the expression levels of clic2 in selected osmoregulatory organs of tilapia, acclimated to freshwater, seawater and hypersaline water. Structural conservation of vertebrate CLICs implies that they might play conserved roles...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29190973/clca4-inhibits-bladder-cancer-cell-proliferation-migration-and-invasion-by-suppressing-the-pi3k-akt-pathway
#10
Teng Hou, Lijie Zhou, Longwang Wang, Gallina Kazobinka, Xiaoping Zhang, Zhaohui Chen
Calcium activated chloride channel A4 (CLCA4), a tumor suppressor, was shown to contribute to the progression of several human cancers, while its role in bladder carcinoma remains unclear. In this study, we showed CLCA4 expression was down-regulated in bladder carcinoma tissues and cells compared to adjacent non-tumor tissues and normal urothelial cells. Low CLCA4 expression was correlated with larger tumor size, advanced tumor stage, and poor prognosis in bladder carcinoma patients. Overexpression of CLCA4 profoundly attenuated the proliferation, growth, migratory and invasive capabilities of bladder cancer cells, whereas CLCA4 knockdown had the opposite effect...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187363/trpv4-heats-up-ano1-dependent-exocrine-gland-fluid-secretion
#11
Sandra Derouiche, Yasunori Takayama, Masataka Murakami, Makoto Tominaga
Several ion channels and transporters regulate fluid secretion in salivary and lacrimal glands. In salivary glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations...
November 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29186788/neurotoxic-effects-of-linalool-and-%C3%AE-pinene-on-tribolium-castaneum-herbst
#12
(no author information available yet)
Effective, ethical pest control requires the use of chemicals that are highly specific, safe, and ecofriendly. Linalool and β-pinene occur naturally as major constituents of the essential oils of many plant species distributed throughout the world, and thus meet these requirements. These monoterpenes were tested as repellents against Tribolium castaneum, using the area preference method, after four hours of exposure and the effect transcriptional of genes associated with neurotransmission. Changes in gene expression of acetylcholinesterase (Ace1), GABA-gated anion channel splice variant 3a6a (Rdl), GABA-gated ion channel (Grd), glutamate-gated chloride channel (Glucl), and histamine-gated chloride channel 2 (Hiscl2) were assessed and the interaction with proteins important for the insect using in silico methods was also studied...
November 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29185178/vasorelaxant-activities-and-the-underlying-pharmacological-mechanisms-of-gynura-procumbens-merr-leaf-extracts-on-rat-thoracic-aorta
#13
Zafar Iqbal, Idris Bello, Mohd Zaini Asmawi, Majed Ahmed Al-Mansoub, Ashfaq Ahmad, Qaiser Jabeen, Yam Mun Fei
Previous studies have investigated the cardiovascular activity of Gynura procumbens Merr. single-solvent extracts. The objective of this study was to evaluate the in vitro vasorelaxant properties and the underlying pharmacological mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves of GP were serially extracted with petroleum ether, chloroform, methanol and water using the maceration method. Suspended aortic ring preparations were pre-contracted with phenylephrine (PE 1 µM), followed by cumulative addition of GP extracts (0...
November 28, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29183375/rdl-mutations-predict-multiple-insecticide-resistance-in-anopheles-sinensis-in-guangxi-china
#14
Chan Yang, Zushi Huang, Mei Li, Xiangyang Feng, Xinghui Qiu
BACKGROUND: Anopheles sinensis is a major vector of malaria in China. The gamma-aminobutyric acid (GABA)-gated chloride channel, encoded by the RDL (Resistant to dieldrin) gene, is the important target for insecticides of widely varied structures. The use of various insecticides in agriculture and vector control has inevitably led to the development of insecticide resistance, which may reduce the control effectiveness. Therefore, it is important to investigate the presence and distribution frequency of the resistance related mutation(s) in An...
November 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29182846/highly-efficient-thin-film-transistor-via-cross-linking-of-1t-edge-functional-2h-molybdenum-disulfides
#15
Hanleem Lee, Sora Bak, Sung-Jin An, Jung Ho Kim, Eunbhin Yun, Meeree Kim, Sohyeon Seo, Mun Seok Jeong, Hyoyoung Lee
Thin film transistors (TFTs) have been received great attention for use in lightweight, large area, and wearable devices. However, the low crystalline materials or inhomogeneous film formation limits a high electrical property of channel for a commercial TFT, especially for flexible electronics. Here, we report a field effect TFT fabricated via a cross-linking of novel edge-1T basal-2H MoS2sheets that are prepared by an edge functional exfoliation of bulk MoS2 with soft organic exfoliation reagents. For novel edge functional exfoliation, the electrophilic 4-carboxy-benzenediazonium used as the soft organic reagent attacks the nucleophilic thiolates exposed at the edge of the bulk MoS2 with a help of an amine catalyst, providing 1T edge-functional HOOC-benzene-2H basal MoS2 nanosheets (e-MoS2)...
November 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/29182412/the-effect-of-water-loading-on-acute-weight-loss-following-fluid-restriction-in-combat-sports-athletes
#16
Reid Reale, Gary Slater, Ian C Dunican, Gregory R Cox, Louise M Burke
Novel methods of acute weight loss practiced by combat sport athletes include 'water loading’; the consumption of large fluid volumes for several days prior to restriction. We examined claims this technique increases total body water losses, while also assessing the risk of hyponatremia. Male athletes were separated into control (CON, n=10) and water loading (WL, n=11) groups and fed a standardised energy-matched diet for 6 days. Day 1-3 fluid intake was 40 mL·kg-1 and 100 mL·kg-1 for CON and WL, respectively with both groups consuming 15 mL·kg-1on Day 4 and following the same rehydration protocol on Days 5-6...
November 28, 2017: International Journal of Sport Nutrition and Exercise Metabolism
https://www.readbyqxmd.com/read/29180450/knockout-of-mitochondrial-voltage-dependent-anion-channel-type-3-increases-reactive-oxygen-species-ros-levels-and-alters-renal-sodium-transport
#17
Li Zou, Valerie Linck, Yu-Jia Zhai, Laura Galarza-Paez, Linda Li, Qiang Yue, Otor Al-Khalili, Hui-Fang Bao, He-Ping Ma, Tiffany L Thai, Jundong Jiao, Douglas C Eaton
It has been suggested that voltage-dependent anion channels (VDACs) control the release of superoxide from mitochondria. We have previously shown that reactive oxygen species (ROS) such as superoxide (O2-) and hydrogen peroxide (H2O2) stimulate epithelial sodium channels (ENaCs) in sodium-transporting epithelial tissue including cortical collecting duct (CCD) principal cells. Therefore, we hypothesized that VDACs could regulate ENaC by modulating cytosolic ROS levels. Herein, we find that VDAC3-knockout(KO) mice can maintain normal salt and water balance on low-salt and high-salt diets...
November 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29176568/low-temperature-fabrication-of-an-hfo2-passivation-layer-for-amorphous-indium-gallium-zinc-oxide-thin-film-transistors-using-a-solution-process
#18
Seonghwan Hong, Sung Pyo Park, Yeong-Gyu Kim, Byung Ha Kang, Jae Won Na, Hyun Jae Kim
We report low-temperature solution processing of hafnium oxide (HfO2) passivation layers for amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). At 150 °C, the hafnium chloride (HfCl4) precursor readily hydrolyzed in deionized (DI) water and transformed into an HfO2 film. The fabricated HfO2 passivation layer prevented any interaction between the back surface of an a-IGZO TFT and ambient gas. Moreover, diffused Hf4+ in the back-channel layer of the a-IGZO TFT reduced the oxygen vacancy, which is the origin of the electrical instability in a-IGZO TFTs...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167417/loss-of-activity-mutation-in-the-cardiac-chloride-bicarbonate-exchanger-ae3-causes-short-qt-syndrome
#19
Kasper Thorsen, Vibeke S Dam, Kasper Kjaer-Sorensen, Lisbeth N Pedersen, V Arvydas Skeberdis, Jonas Jurevičius, Rimantas Treinys, Ida M B S Petersen, Morten S Nielsen, Claus Oxvig, J Preben Morth, Vladimir V Matchkov, Christian Aalkjær, Henning Bundgaard, Henrik K Jensen
Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167013/bovine-oviductal-and-uterine-fluid-support-in-vitro-embryo-development
#20
Meriem Hamdi, Ricaurte Lopera-Vasquez, Veronica Maillo, Maria Jesus Sanchez-Calabuig, Carolina Núnez, Alfonso Gutierrez-Adan, Dimitrios Rizos
In order to mimic the maternal oviductal environment, we evaluated the effect of oviductal fluid (OF) and/or uterine fluid (UF) supplementation on in vitro embryo development and quality. In vitro-produced zygotes were cultured with 1.25% OF from Day 1 to Day 4 after insemination (OF group), 1.25% OF from Day 1 to Day 4 followed by 1.25% UF from Day 4 to Day 9 (OF+UF group) or 1.25% UF only from Day 4 to Day 9 (UF group). Control groups were cultured in the presence of synthetic oviduct fluid (SOF) supplemented with 3mgmL-1 bovine serum albumin (BSA) or 5% fetal calf serum (FCS)...
November 23, 2017: Reproduction, Fertility, and Development
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