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https://www.readbyqxmd.com/read/28899969/tmem16a-ano1-inhibits-apoptosis-via-down-regulation-of-bim-expression
#1
Neal R Godse, Nayel I Khan, Zachary A Yochum, Roberto Gomez-Casal, Carolyn Kemp, Daniel J Shiwarski, Raja Seethala, Scott Kulich, Mukund Seshadri, Timothy F Burns, Umamaheswar Duvvuri
PURPOSE: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCC), raising the possibility of an anti-apoptotic role in malignant cells. The present study investigated this using a multi-modal, translational investigation. EXPERIMENTAL DESIGN: Combination of 1) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression 2) in vivo studies assessing similar outcomes, and 3) molecular and staining analysis of human HNSCC samples...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28861046/genomic-physiologic-and-symbiotic-characterization-of-serratia-marcescens-strains-isolated-from-the-mosquito-anopheles-stephensi
#2
Shicheng Chen, Jochen Blom, Edward D Walker
Strains of Serratia marcescens, originally isolated from the gut lumen of adult female Anopheles stephensi mosquitoes, established persistent infection at high rates in adult A. stephensi whether fed to larvae or in the sugar meal to adults. By contrast, the congener S. fonticola originating from Aedes triseriatus had lower infection in A. stephensi, suggesting co-adaptation of Serratia strains in different species of host mosquitoes. Coinfection at high infection rate in adult A. stephensi resulted after feeding S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28800723/a-clca-regulatory-protein-present-in-the-chemosensory-cilia-of-olfactory-sensory-neurons-induces-a-ca-2-activated-cl-current-when-transfected-into-hek293
#3
Casilda V Mura, Ricardo Delgado, María Graciela Delgado, Diego Restrepo, Juan Bacigalupo
BACKGROUND: CLCA is a family of metalloproteases that regulate Ca(2+)-activated Cl(-) fluxes in epithelial tissues. In HEK293 cells, CLCA1 promotes membrane expression of an endogenous Anoctamin 1 (ANO1, also termed TMEM16A)-dependent Ca(2+)-activated Cl(-) current. Motif architecture similarity with CLCA2, 3 and 4 suggested that they have similar functions. We previously detected the isoform CLCA4L in rat olfactory sensory neurons, where Anoctamin 2 is the principal chemotransduction Ca(2+)-activated Cl(-) channel...
August 11, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#4
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28733893/effects-of-new-generation-tmem16a-inhibitors-on-calcium-activated-chloride-currents-in-rabbit-urethral-interstitial-cells-of-cajal
#5
Stephen Fedigan, Eamonn Bradley, Timothy Webb, Roddy J Large, Mark A Hollywood, Keith D Thornbury, Noel G McHale, Gerard P Sergeant
Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit Ca(2+)-activated Cl(-) currents (I ClCa) that are important for the development of urethral tone. Here, we examined if TMEM16A (ANO1) contributed to this activity by examining the effect of "new-generation" TMEM16A inhibitors, CACCinh-A01 and T16Ainh-A01, on I ClCa recorded from freshly isolated rabbit urethral ICC (RUICC) and on contractions of intact strips of rabbit urethra smooth muscle. Real-time quantitative PCR experiments demonstrated that TMEM16A was highly expressed in rabbit urethra smooth muscle, in comparison to TMEM16B and TMEM16F...
July 21, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28685234/prostanoid-ep3-receptor-agonist-sulprostone-enhances-pacemaker-activity-of-colonic-interstitial-cells-of-cajal
#6
Man Woo Kim, Han Yi Jiao, Seok Won Kim, Chan Guk Park, Mei Jin Wu, Chansik Hong, Seok Choi, Jae Yeoul Jun
EP receptor activation by PGE2 regulates gastrointestinal motility by modulating smooth muscle contractility. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate smooth muscle activity. We aimed to determine effects of the EP3 receptor agonist sulprostone on pacemaker potentials in colonic ICCs. We performed a whole cell patch clamp, RT-PCR, and Ca(2+) imaging in cultured ICCs from mouse colon. Sulprostone depolarized the membrane and increased pacemaker frequency. EP3 receptor antagonist blocked these sulprostone-induced effects...
July 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28666267/cell-specific-regulation-of-proliferation-by-ano1-tmem16a-in-breast-cancer-with-different-er-pr-and-her2-status
#7
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)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648509/pendred-syndrome
#8
REVIEW
Jean-Louis Wémeau, Peter Kopp
Pendred syndrome is an autosomal recessive disorder that is classically defined by the combination of sensorineural deafness/hearing impairment, goiter, and an abnormal organification of iodide with or without hypothyroidism. The hallmark of the syndrome is the impaired hearing, which is associated with inner ear malformations such as an enlarged vestibular aqueduct (EVA). The thyroid phenotype is variable and may be modified by the nutritional iodine intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4/PDS gene, which encodes the multifunctional anion exchanger pendrin...
March 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28642338/cellular-distribution-and-function-of-ion-channels-involved-in-transport-processes-in-rat-tracheal-epithelium
#9
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
#10
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
#11
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...
July 3, 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
#12
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
#13
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
#14
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...
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
#15
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)...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28488023/glucose-enhances-rotavirus-enterotoxin-induced-intestinal-chloride-secretion
#16
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
#17
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
#18
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
#19
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
#20
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
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