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Trey S Rottgen, Andrew J Nickerson, Emily A Minor, Amanda B Stewart, Abby D Harold, Vazhaikkurichi M Rajendran
Attenuated Ca2+ -activated Cl- secretion has previously been observed in the model of dextran-sulfate-sodium (DSS)-induced colitis. Prior studies have implicated dysfunctional muscarinic signaling from basolateral membranes as the potential perpetrator leading to decreased Ca2+ -activated Cl- secretion. However, in our chronic model of DSS-colitis, Chrm3 transcript (1.028 {plus minus} 0.12 vs. 1.029 {plus minus} 0.27, p > 0.05) and CHRM3 protein expression (1.021 {plus minus} .24 vs. .928 {plus minus} .09, p > 0...
March 21, 2018: American Journal of Physiology. Cell Physiology
Jonathon P Misiewicz, Sarah N Elliott, Kevin B Moore, Henry F Schaefer
Stabilized Criegee intermediates (SCI) are formed during the ozonolysis of unsaturated hydrocarbons and have been implicated in the formation of hydroxyl radicals and aerosols. Previous theoretical research [S. Jørgenson and A. Gross, J. Phys. Chem. A, 2009, 113, 10284-10290] computed the rate constants for addition of ammonia to simple SCIs, but reported a wide distribution of quantum chemical energies, depending on the basis set used. We report optimized geometries for these reactions at the CCSD(T)/ANO2 and CCSD(T)/ANO1 levels, and CCSD(T)/CBS energies with perturbative quadruples corrections...
February 28, 2018: Physical Chemistry Chemical Physics: PCCP
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
Antonio De la Vieja, Pilar Santisteban
Iodide (I- ) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I- is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I- recycling...
April 2018: Endocrine-related Cancer
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
Jun Sang Bae, Jeong Yeol Park, See-Hyoung Park, Sang Hoon Ha, Ae Ri An, Sang Jae Noh, Keun Sang Kwon, Sung Hoo Jung, Ho Sung Park, Myoung Jae Kang, Kyu Yun Jang
The expression of ANO1 is considered to have diagnostic specificity for gastrointestinal stromal tumors. However, its function as a calcium-activated chloride channel suggests that the expression of ANO1 is not restricted to gastrointestinal stromal tumors. Recently, it has been reported that ANO1 has roles in the progression of human malignant tumors. However, the role of ANO1 in breast carcinoma has been controversial. Therefore, we investigated the expression of ANO1 in 139 breast carcinoma patients and the role of ANO1 in vitro ...
January 2, 2018: Oncotarget
Jonghyun Choi, Yongwoo Jang, Haedong Kim, Jungwon Wee, Sinyoung Cho, Woo Sung Son, Sung Min Kim, Young Duk Yang
Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2+ and noxious heat...
January 16, 2018: BMB Reports
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
José J De Jesús-Pérez, Silvia Cruz-Rangel, Ángeles E Espino-Saldaña, Ataúlfo Martínez-Torres, Zhiqiang Qu, H Criss Hartzell, Nancy E Corral-Fernandez, Patricia Pérez-Cornejo, Jorge Arreola
The TMEM16A-mediated Ca2+-activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+...
December 22, 2017: Biochimica et Biophysica Acta
Safinur Atay, Daniel W Wilkey, Mohammed Milhem, Michael Merchant, Andrew K Godwin
Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity. In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT. Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules...
March 2018: Molecular & Cellular Proteomics: MCP
Peter R Franke, Gary E Douberly
Isoprene (C5 H8 ) is an abundant, reactive tropospheric hydrocarbon, derived from biogenic emissions. A detailed understanding of the spectroscopy of isoprene is therefore desirable. Isoprene monomer is isolated in helium droplets and its infrared spectrum is measured in the CH stretching region. Anharmonic frequencies are predicted by VPT2+K simulations employing CCSD(T) force fields with quadratic (cubic and quartic) force constants computed using the ANO1 (ANO0) basis set. The vast majority of the spectral features can be assigned to trans-isoprene on the basis of these computations...
January 11, 2018: Journal of Physical Chemistry. A
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...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Huizhe Wu, Hui Wang, Shu Guan, Jing Zhang, Qiuchen Chen, Xiaodong Wang, Ke Ma, Pengfei Zhao, Haishan Zhao, Weifan Yao, Feng Jin, Qinghuan Xiao, Minjie Wei
The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)...
October 17, 2017: Oncotarget
Joana R Lérias, Madalena C Pinto, Hugo M Botelho, Nikhil T Awatade, Margarida C Quaresma, Iris A L Silva, Podchanart Wanitchakool, Rainer Schreiber, Rainer Pepperkok, Karl Kunzelmann, Margarida D Amaral
An attractive possibility to treat Cystic Fibrosis (CF), a severe condition caused by dysfunctional CFTR, an epithelial anion channel, is through the activation of alternative (non-CFTR) anion channels. Anoctamin 1 (ANO1) was demonstrated to be a Ca2+ -activated chloride channel (CaCC) and thus of high potential to replace CFTR. Despite that ANO1 is expressed in human lung CF tissue, it is present at the cell surface at very low levels. In addition, little is known about regulation of ANO1 traffic, namely which factors promote its plasma membrane (PM) localization...
February 2018: Biochimica et Biophysica Acta
Rainer Schreiber, Jiraporn Ousingsawat, Podchanart Wanitchakool, Lalida Sirianant, Roberta Benedetto, Karina Reiss, Karl Kunzelmann
TMEM16/anoctamin proteins form Ca(2+) activated ion channels or phospholipid scramblases. We found that both TMEM16A/ANO1 and TMEM16F/ANO6 produced Cl(-) currents when activated by intracellular Ca(2+) , but only TMEM16F was able to expose phosphatidylserine to the outer leaflet of the plasma membrane. Mutations within TMEM16F or TMEM16A/F chimeras similarly changed Cl(-) currents and phospholipid scrambling, suggesting the same intramolecular pathway for Cl(-) and phospholipids. When overexpressed, TMEM16A and TMEM16F produced spontaneous Cl(-) currents at 37°C even at resting intracellular Ca(2+) levels, which was abolished by inhibition of phospholipase A2 (PLA2 )...
November 14, 2017: Journal of Physiology
Andrey Finegersh, Scott Kulich, Theresa Guo, Alexander V Favorov, Elana J Fertig, Ludmila V Danilova, Daria A Gaykalova, Joseph A Califano, Umamaheswar Duvvuri
ANO1 is a calcium-activated chloride channel that is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and other cancers. While ANO1 expression negatively correlates with survival in several cancers, its epigenetic regulation is poorly understood. We analyzed HNSCC samples from TCGA and a separate dataset of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples to identify differentially methylated regions. E6 and E7 transfected normal oral keratinocytes (NOK) were used to induce hypermethylation of the ANO1 promoter...
November 9, 2017: Scientific Reports
Ayed M Allawzi, Alexander Vang, Richard T Clements, Bong Sook Jhun, Nouaying R Kue, Thomas J Mancini, Amy K Landi, Dmitry Terentyev, Jin O-Uchi, Suzy A Comhair, Serpil C Erzurum, Gaurav Choudhary
Hyperproliferative endothelial cells (ECs) play an important role in the pathogenesis of PAH. Anoctamin-1 (Ano1), a calcium activated chloride channel, can regulate cell proliferation and cell cycle in multiple cell types. However, the expression and function of Ano1 in the pulmonary endothelium is unknown. We examined whether Ano1 was expressed in pulmonary ECs and if altering Ano1 activity would affect EC survival. Expression and localization of Ano1 in rat lung microvascular ECs (RLMVECs) was assessed using immunoblot, immunofluorescence, and subcellular fractionation...
November 3, 2017: American Journal of Respiratory Cell and Molecular Biology
Anna Qian, Shawn Means, Leo K Cheng, James Sneyd, Peng Du
The interstitial cells of Cajal (ICC) generate electrophysiological events called slow waves that regulate the motility of the gastrointestinal (GI) tract. Recent studies have demonstrated that the Ca(2+)-activated Cl(-) -channel, encoded by the anoctamin1 (Ano1) protein, has a major role in regulating intestinal slow waves and motility. The main aim of this study was to develop a multi-scale mathematical model capable of simulating both normal slow wave entrainment and the effects of Ano1 knockout (KO) on the normal activity...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
B P Herring, A M Hoggatt, A Gupta, S Griffith, A Nakeeb, J N Choi, M T Idrees, T Nowak, D L Morris, J M Wo
BACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis...
October 20, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Roberta Benedetto, Jiraporn Ousingsawat, Podchanart Wanitchakool, Yong Zhang, Michael J Holtzman, Margarida Amaral, Jason R Rock, Rainer Schreiber, Karl Kunzelmann
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in airways and intestine that is activated through ATP binding and phosphorylation by protein kinase A, but fails to operate in cystic fibrosis (CF). TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca(2+) activated secretory chloride channel independent of CFTR. Here we report that tissue specific knockout of the TMEM16A gene in mouse intestine and airways not only eliminates Ca(2+)-activated Cl(-) currents, but unexpectedly also abrogates CFTR-mediated Cl(-) secretion and completely abolishes cAMP-activated whole cell currents...
September 29, 2017: Scientific Reports
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