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https://www.readbyqxmd.com/read/28642338/cellular-distribution-and-function-of-ion-channels-involved-in-transport-processes-in-rat-tracheal-epithelium
#1
Anne Hahn, Johannes Faulhaber, Lalita Srisawang, Andreas Stortz, Johanna J Salomon, Marcus A Mall, Stephan Frings, Frank Möhrlen
Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca(2+) or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca(2+)- dependent and cAMP- dependent Cl(-) secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca(2+)-gated Cl(-) channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, the epithelial Na(+) channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28620305/comparative-effects-of-chloride-channel-inhibitors-on-lrrc8-vrac-mediated-chloride-conductance
#2
Jonas Friard, Michel Tauc, Marc Cougnon, Vincent Compan, Christophe Duranton, Isabelle Rubera
Chloride channels play an essential role in a variety of physiological functions and in human diseases. Historically, the field of chloride channels has long been neglected owing to the lack of powerful selective pharmacological agents that are needed to overcome the technical challenge of characterizing the molecular identities of these channels. Recently, members of the LRRC8 family have been shown to be essential for generating the volume-regulated anion channel (VRAC) current, a chloride conductance that governs the regulatory volume decrease (RVD) process...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28592421/clustering-of-ca-2-transients-in-interstitial-cells-of-cajal-defines-slow-wave-duration
#3
Bernard T Drumm, Grant W Hennig, Matthew J Battersby, Erin K Cunningham, Tae Sik Sung, Sean M Ward, Kenton M Sanders, Salah A Baker
Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca(2+)-activated Cl(-) channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca(2+) regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca(2+) transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca(2+) sensor, GCaMP3, in ICC...
June 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28588500/temporal-expression-patterns-of-clock-genes-and-aquaporin-5-anoctamin-1-in-rat-submandibular-gland-cells
#4
Ryouichi Satou, Masaki Sato, Maki Kimura, Yoichi Ishizuka, Masakazu Tazaki, Naoki Sugihara, Yoshiyuki Shibukawa
Circadian rhythms are essential for health and regulate various physiological functions. These rhythms are regulated by a negative-feedback loop involving clock genes in the suprachiasmatic nucleus (SCN) and peripheral tissues. The rate of secretion of salivary substances, ions, and water follows a circadian rhythm, however, the relationship between the molecular mechanism of salivary secretion and peripheral circadian rhythm is not yet clear. Anoctamin 1 (ANO1, also known as TMEM16A) and Aquaporin 5 (AQP5) play an important role in the transport of ions and water in the submandibular glands (SGs)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28539652/ano1-inhibits-cardiac-fibrosis-after-myocardial-infraction-via-tgf-%C3%AE-smad3-pathway
#5
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/28537131/acupuncture-ameliorates-postoperative-ileus-via-il-6-mir-19a-kit-axis-to-protect-interstitial-cells-of-cajal
#6
Jingjing Deng, Shu Yang, Qing Yuan, Yuzhong Chen, Dandan Li, Haimei Sun, Xinghua Tan, Fuchun Zhang, Deshan Zhou
Acupuncture is a therapy effective in treating postoperative ileus (POI); its underlying mechanisms remain unclear. MicroRNAs (miRNAs) participate in inflammation and injury to the interstitial cells of Cajal (ICCs), both of which are considered to be contributors to POI. C-kit, encoding KIT, a specific marker of ICCs, is predicted to be targeted by miR-19a, an inflammation-related miRNA. Therefore, we investigated a possible link between inflammation, miR-19a, and ICCs in POI, as well as the mechanism by which these factors are affected by acupuncture...
May 24, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28493701/substituted-2-acylaminocycloalkylthiophene-3-carboxylic-acid-arylamides-as-inhibitors-of-the-calcium-activated-chloride-channel-transmembrane-protein-16a-tmem16a
#7
Eric C Truong, Puay W 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-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa)...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28488023/glucose-enhances-rotavirus-enterotoxin-induced-intestinal-chloride-secretion
#8
Liangjie Yin, Rejeesh Menon, Reshu Gupta, Lauren Vaught, Paul Okunieff, Sadasivan Vidyasagar
Rotavirus causes severe diarrhea in small children and is typically treated using glucose-containing oral rehydration solutions; however, glucose may have a detrimental impact on these patients, because it increases chloride secretion and presumably water loss. The rotavirus enterotoxin nonstructural protein 4 (NSP4) directly inhibits glucose-mediated sodium absorption. We examined the effects of NSP4 and glucose on sodium and chloride transport in mouse small intestines and Caco-2 cells. Mouse small intestines and Caco-2 cells were incubated with NSP4114-135 in the presence/absence of glucose...
May 10, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28420732/modulation-of-tmem16a-channel-activity-by-the-von-willebrand-factor-type-a-vwa-domain-of-the-calcium-activated-chloride-channel-regulator-1-clca1
#9
Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Colin G Nichols, Tom J Brett
Calcium-activated chloride channels (CaCCs) are key players in transepithelial ion transport and fluid secretion, smooth muscle constriction, neuronal excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surface, but the exact mechanism is unknown. Here we demonstrate that the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal fragment is necessary and sufficient for this interaction...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28413214/circulating-biomarkers-for-predicting-infliximab-response-in-rheumatoid-arthritis-a-systematic-bioinformatics-analysis
#10
Qiu-Lan Huang, Fu-Jiang Zhou, Cheng-Bin Wu, Chao Xu, Wen-Ying Qian, De-Ping Fan, Xu-Shan Cai
BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid arthritis (RA). However, many patients responded poorly and related studies were inconsistent in predictive biomarkers. This study aimed to identify circulating biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for related microarray datasets, focused on the response to infliximab in RA. All peripheral blood samples were collected before infliximab treatment and gene expression profiles were measured using microarray...
April 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28401775/semi-automatic-bowel-wall-thickness-measurements-on-mr-enterography-in-patients-with-crohn-s-disease
#11
Robiel E Naziroglu, Carl A J Puylaert, Jeroen A W Tielbeek, Jesica Makanyanga, Alex Menys, Cyriel Y Ponsioen, Haralambos Hatzakis, Stuart A Taylor, Jaap Stoker, Lucas J van Vliet, Frans M Vos
OBJECTIVE: To evaluate a semi-automatic method for delineation of the bowel wall and measurement of the wall thickness in patients with Crohn's disease. METHODS: 53 patients with suspected or proven Crohn's disease were selected. Two radiologists independently supervised the delineation of regions with active Crohn's disease on MRI, yielding manual annotations (Ano1, Ano2). Three observers manually measured the maximal bowel wall thickness of each annotated segment...
June 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28362855/inhibition-of-ano1-by-luteolin-and-its-cytotoxicity-in-human-prostate-cancer-pc-3-cells
#12
Yohan Seo, Kunhi Ryu, Jinhong Park, Dong-Kyu Jeon, Sungwoo Jo, Ho K Lee, Wan Namkung
Anoctamin 1 (ANO1), a calcium-activated chloride channel, is highly amplified in prostate cancer, the most common form of cancer and leading causes of cancer death in men, and downregulation of ANO1 expression or its functional activity is known to inhibit cell proliferation, migration and invasion in prostate cancer cells. Here, we performed a cell-based screening for the identification of ANO1 inhibitors as potential anticancer therapeutic agents for prostate cancer. Screening of ~300 selected bioactive natural products revealed that luteolin is a novel potent inhibitor of ANO1...
2017: PloS One
https://www.readbyqxmd.com/read/28336549/eavk-segment-c-sequence-confers-ca-2-dependent-changes-to-the-kinetics-of-full-length-human-ano1
#13
Peter R Strege, Simon J Gibbons, Amelia Mazzone, Cheryl E Bernard, Arthur Beyder, Gianrico Farrugia
Anoctamin1 (Ano1 and TMEM16A) is a calcium-activated chloride channel specifically expressed in the interstitial cells of Cajal (ICC) of the gastrointestinal tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full-length human Ano1 sequence includes an additional exon, exon "0," at the NH2 terminus. Ano1 with exon 0 [Ano1(0)] had a lower EC50 for intracellular calcium ([Ca(2+)]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter ICl at low [Ca(2+)]i Exon 13 is expressed in 75-100% of Ano1 transcripts in most human tissues but only 25% in the human stomach...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28315973/stem-cell-factor-kit-signal-insufficiency-contributes-to-hypoxia-induced-intestinal-motility-dysfunctions-in-neonatal-mice
#14
Hong Ren, Juan Han, Zhifang Li, Zhiyong Xiong
BACKGROUND: Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear. METHODS: Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+)...
May 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28299581/expression-of-anoctamin-1-is-associated-with-advanced-tumor-stage-in-patients-with-non-small-cell-lung-cancer-and-predicts-recurrence-after-surgery
#15
Y He, H Li, Y Chen, P Li, L Gao, Y Zheng, Y Sun, J Chen, X Qian
PURPOSE: Anoctamin 1 (ANO1), a recently identified calcium-activated chloride channel, has been found to have a critical role in tumorigenesis and tumor progression in several types of cancer. However, its role in non-small cell lung cancer (NSCLC) remains to be elucidated. In this study, we evaluated the utility of ANO1 as a prognostic marker. PATIENTS AND METHODS: ANO1 expression was detected in tumor tissues and paraneoplastic tissues of I-IV stage NSCLC patients who received surgical treatment by using immunohistochemical and quantitative RT-PCR analyses...
March 15, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28293832/the-mechanistic-role-of-the-calcium-activated-chloride-channel-ano1-in-tumor-growth-and-signaling
#16
Anke Bill, Larry Alex Gaither
Multiple studies have described the high expression and amplification of Anoctamin 1 (ANO1) in various cancers, including, but not limited to breast cancer, head and neck cancer, gastrointestinal stromal tumors and glioblastoma. ANO1 has been demonstrated to be critical for tumor growth in breast and head and neck cancers through its regulation of EGFR signaling and pathway modulators like MAPK and protein kinase B. However, the discovery of ANO1 as a calcium activated chloride channel came as a surprise to the field and has given rise to many questions...
March 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28288036/gist-manifesting-as-a-retroperitoneal-tumor-clinicopathologic-immunohistochemical-and-molecular-genetic-study-of-112-cases
#17
Markku Miettinen, Anna Felisiak-Golabek, Zengfeng Wang, Shingo Inaguma, Jerzy Lasota
Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal (GI) tract, but some present apparently outside the GI tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21 to 89 y). On the basis of clinically or histologically detected connections to GI tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n=25), pelvic (n=11), mesenteric (n=4), and of unspecified/miscellaneous sites (n=35)...
May 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28225032/4-isopropylcyclohexanol-has-potential-analgesic-effects-through-the-inhibition-of-anoctamin-1-trpv1-and-trpa1-channel-activities
#18
Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203258/electroacupuncture-at-st36-protects-icc-networks-via-mscf-kit-etv1-signaling-in-the-stomach-of-diabetic-mice
#19
Lugao Tian, Beibei Zhu, Shi Liu
Background. Electroacupuncture (EA) at ST36 has been used to regulate gastric motility and effectively improve gastric emptying in diabetic patients. Nevertheless, the specific mechanisms underlying the efficacy of this treatment remain unknown. The aim of this study was to assess the variations of interstitial cells of Cajal (ICC) and explore the changes in mSCF/KIT-ETV1 signaling in the antrum and corpus of diabetic mice after treatment with EA. Methods. Male C57BL/6 mice were randomized into five groups: control group, diabetic group (DM), diabetic-plus-sham EA group (SEA), diabetic-plus-low-frequency EA group (LEA), and diabetic-plus-high-frequency EA group (HEA)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28183802/differential-effects-of-anoctamins-on-intracellular-calcium-signals
#20
Inês Cabrita, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V Skryabin, Laura K Schenk, Hermann Pavenstädt, Rainer Schreiber, Karl Kunzelmann
The Ca(2+) activated Cl(-) channel TMEM16A [anoctamin (ANO)1] is homologous to yeast Ist2 and has been shown to tether the cortical endoplasmic reticulum (ER) to the plasma membrane. We therefore examined whether ANO1 and other members of the ANO family affect intracellular Ca(2+) ([Ca(2+)]i) signals. It is shown that expression of ANO1 augments Ca(2+) store release upon stimulation of GPCRs, whereas knockdown of ANO1, or lack of Ano1 expression in Ano1(-/-) animals as shown in an earlier report, inhibits Ca(2+) release...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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