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  1 / 8062 MEDLINE  
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[PMID]:29346439
[Au] Autor:Mundhenk L; Erickson NA; Klymiuk N; Gruber AD
[Ad] Endereço:Department of Veterinary Pathology, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
[Ti] Título:Interspecies diversity of chloride channel regulators, calcium-activated 3 genes.
[So] Source:PLoS One;13(1):e0191512, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Members of the chloride channel regulators, calcium-activated (CLCA) family, have been implicated in diverse biomedical conditions, including chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, the activation of macrophages, and the growth and metastatic spread of tumor cells. Several observations, however, could not be repeated across species boundaries and increasing evidence suggests that select CLCA genes are particularly prone to dynamic species-specific evolvements. Here, we systematically characterized structural and expressional differences of the CLCA3 gene across mammalian species, revealing a spectrum of gene duplications, e.g., in mice and cows, and of gene silencing via diverse chromosomal modifications in pigs and many primates, including humans. In contrast, expression of a canonical CLCA3 protein from a single functional gene seems to be evolutionarily retained in carnivores, rabbits, guinea pigs, and horses. As an accepted asthma model, we chose the cat to establish the tissue and cellular expression pattern of the CLCA3 protein which was primarily found in mucin-producing cells of the respiratory tract and in stratified epithelia of the esophagus. Our results suggest that, among developmental differences in other CLCA genes, the CLCA3 gene possesses a particularly high dynamic evolutionary diversity with pivotal consequences for humans and other primates that seem to lack a CLCA3 protein. Our data also help to explain previous contradictory results on CLCA3 obtained from different species and warrant caution in extrapolating data from animal models in conditions where CLCA3 may be involved.
[Mh] Termos MeSH primário: Canais de Cloreto/fisiologia
[Mh] Termos MeSH secundário: Animais
Canais de Cloreto/classificação
Evolução Molecular
Família Multigênica
Filogenia
Doenças Respiratórias/genética
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chloride Channels)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191512


  2 / 8062 MEDLINE  
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[PMID]:28452066
[Au] Autor:Zhang X; Li H; Zhang H; Liu Y; Huo L; Jia Z; Xue Y; Sun X; Zhang W
[Ad] Endereço:Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
[Ti] Título:Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.
[So] Source:Br J Pharmacol;174(14):2334-2345, 2017 Jul.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective and anticancer effects. Transmembrane member 16A (TMEM16A)-encoded Ca -activated Cl channels play a variety of physiological roles in many organs and tissues. Overexpression of TMEM16A is also believed to be associated with cancer progression. Therefore, inhibition of TMEM16A current may be a potential target for cancer therapy. In this study, we screened a broad spectrum of flavonoids for their inhibitory activities on TMEM16A currents. EXPERIMENTAL APPROACH: A whole-cell patch technique was used to record the currents. The BrdU assay and transwell technique were used to investigate cell proliferation and migration. KEY RESULTS: At a concentration of 100 µM, 10 of 20 compounds caused significant (>50%) inhibition of TMEM16A currents. The four most potent compounds - luteolin, galangin, quercetin and fisetin - had IC values ranging from 4.5 to 15 µM). To examine the physiological relevance of these findings, we also studied the effects of these flavonoids on endogenous TMEM16A currents in addition to cell proliferation and migration in LA795 cancer cells. Among the flavonoids tested, we detected a highly significant correlation between TMEM16A current inhibition and cell proliferation or reduction of migration. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that flavonoids inhibit TMEM16A currents and suggests that flavonoids could have anticancer effects via this mechanism.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Produtos Biológicos/farmacologia
Canais de Cloreto/antagonistas & inibidores
Flavonoides/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Fitogênicos/química
Produtos Biológicos/química
Células CHO
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Canais de Cloreto/metabolismo
Cricetulus
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Flavonoides/química
Células HEK293
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Biological Products); 0 (Chloride Channels); 0 (Flavonoids)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13841


  3 / 8062 MEDLINE  
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[PMID]:29338044
[Au] Autor:Andley UP; Tycksen E; McGlasson-Naumann BN; Hamilton PD
[Ad] Endereço:Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
[Ti] Título:Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract.
[So] Source:PLoS One;13(1):e0190817, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mammalian eye lens expresses a high concentration of crystallins (α, ß and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts. Several destabilizing mutations in crystallin genes are linked with human autosomal dominant hereditary cataracts. To investigate the mechanism by which the α-crystallin mutations Cryaa-R49C and Cryab-R120G lead to cataract formation, we determined whether these mutations cause an altered expression of specific transcripts in the lens at an early postnatal age by RNA-seq analysis. Using knock-in mouse models previously generated in our laboratory, in the present work, we identified genes that exhibited altered abundance in the mutant lenses, including decreased transcripts for Clic5, an intracellular water channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant lenses, suggesting that the αA-crystallin mutation regulates histone expression via a transcriptional mechanism. Additionally, these studies confirmed the increased expression of histones H2B, H2A, and H4 by proteomic analysis of Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously. Taken together, these findings offer additional insight into the early transcriptional changes caused by Cryaa and Cryab mutations associated with autosomal dominant human cataracts, and indicate that the transcript levels of certain genes are affected by the expression of mutant α-crystallin in vivo.
[Mh] Termos MeSH primário: Catarata/genética
Mutação
Cadeia A de alfa-Cristalina/genética
Cadeia B de alfa-Cristalina/genética
[Mh] Termos MeSH secundário: Animais
Carboxipeptidases/genética
Carboxipeptidases/metabolismo
Catarata/metabolismo
Canais de Cloreto/genética
Canais de Cloreto/metabolismo
Modelos Animais de Doenças
Expressão Gênica
Técnicas de Introdução de Genes
Histonas/genética
Histonas/metabolismo
Seres Humanos
Cristalino/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Mutantes
Camundongos Transgênicos
Proteínas/genética
Proteínas/metabolismo
Proteômica
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Cadeia A de alfa-Cristalina/metabolismo
Cadeia B de alfa-Cristalina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Aebp1 protein, mouse); 0 (CLIC5 protein, mouse); 0 (Chloride Channels); 0 (Cryab protein, mouse); 0 (Histones); 0 (Proteins); 0 (Repressor Proteins); 0 (alpha-Crystallin A Chain); 0 (alpha-Crystallin B Chain); 0 (vig1 protein, mouse); EC 3.4.- (Carboxypeptidases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190817


  4 / 8062 MEDLINE  
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[PMID]:29198705
[Au] Autor:Zeng J; Li Z; Lui EY; Lam SH; Swaminathan K
[Ad] Endereço:Department of Biological Sciences, National University of Singapore 117543, Singapore.
[Ti] Título:Tilapia and human CLIC2 structures are highly conserved.
[So] Source:Biochem Biophys Res Commun;495(2):1752-1757, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. Also, tissue-specific responsiveness of clic2 suggests that it might be involved in iono-osmoregulation under extreme conditions in tilapia.
[Mh] Termos MeSH primário: Canais de Cloreto/química
Canais de Cloreto/genética
Proteínas de Peixes/química
Proteínas de Peixes/genética
Tilápia/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Canais de Cloreto/metabolismo
Sequência Conservada
Proteínas de Peixes/metabolismo
Seres Humanos
Modelos Moleculares
Osmorregulação/genética
Osmorregulação/fisiologia
Filogenia
Conformação Proteica
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Salinidade
Homologia de Sequência de Aminoácidos
Tilápia/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CLIC2 protein, human); 0 (Chloride Channels); 0 (Fish Proteins); 0 (RNA, Messenger)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE


  5 / 8062 MEDLINE  
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[PMID]:29179179
[Au] Autor:Shi R; Xiao ZT; Zheng YJ; Zhang YL; Xu JW; Huang JH; Zhou WL; Li PB; Su WW
[Ad] Endereço:Guangdong Engineering & Technology Research Center for Quality and Efficacy Re-evaluation of Post-market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
[Ti] Título:Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.
[So] Source:Cell Physiol Biochem;44(3):1146-1160, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.
[Mh] Termos MeSH primário: Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo
Células Epiteliais/efeitos dos fármacos
Flavanonas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos de Bário/farmacologia
Benzoatos/farmacologia
Células Cultivadas
Canais de Cloreto/antagonistas & inibidores
Canais de Cloreto/metabolismo
Cloretos/farmacologia
Colforsina/farmacologia
AMP Cíclico/análise
Regulador de Condutância Transmembrana em Fibrose Cística/antagonistas & inibidores
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Células Epiteliais/citologia
Células Epiteliais/metabolismo
Feminino
Seres Humanos
Iminas/farmacologia
Transporte de Íons/efeitos dos fármacos
Masculino
Microscopia de Fluorescência
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
Tiazolidinas/farmacologia
Traqueia/citologia
ortoaminobenzoatos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone); 0 (Barium Compounds); 0 (Benzoates); 0 (Chloride Channels); 0 (Chlorides); 0 (Flavanones); 0 (Imines); 0 (Thiazolidines); 0 (ortho-Aminobenzoates); 0VK51DA1T2 (barium chloride); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1F7A44V6OU (Colforsin); 82985-31-7 (RMI 12330A); 952VN06WBB (fenamic acid); E0399OZS9N (Cyclic AMP); HN5425SBF2 (naringenin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485419


  6 / 8062 MEDLINE  
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[PMID]:29244877
[Au] Autor:Steinmann ME; Schmidt RS; Macêdo JP; Kunz Renggli C; Bütikofer P; Rentsch D; Mäser P; Sigel E
[Ad] Endereço:Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
[Ti] Título:Identification and characterization of the three members of the CLC family of anion transport proteins in Trypanosoma brucei.
[So] Source:PLoS One;12(12):e0188219, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CLC type anion transport proteins are homo-dimeric or hetero-dimeric with an integrated transport function in each subunit. We have identified and partially characterized three members of this family named TbVCL1, TbVCL2 and TbVCL3 in Trypanosoma brucei. Among the human CLC family members, the T. brucei proteins display highest similarity to CLC-6 and CLC-7. TbVCL1, but not TbVCL2 and TbVCL3 is able to complement growth of a CLC-deficient Saccharomyces cerevisiae mutant. All TbVCL-HA fusion proteins localize intracellulary in procyclic form trypanosomes. TbVCL1 localizes close to the Golgi apparatus and TbVCL2 and TbVCL3 to the endoplasmic reticulum. Upon expression in Xenopus oocytes, all three proteins induce similar outward rectifying chloride ion currents. Currents are sensitive to low concentrations of DIDS, insensitive to the pH in the range 5.4 to 8.4 and larger in nitrate than in chloride medium.
[Mh] Termos MeSH primário: Canais de Cloreto/genética
Retículo Endoplasmático/metabolismo
Estágios do Ciclo de Vida/fisiologia
Proteínas de Protozoários/genética
Saccharomyces cerevisiae/metabolismo
Trypanosoma brucei brucei/metabolismo
[Mh] Termos MeSH secundário: Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia
Animais
Canais de Cloreto/antagonistas & inibidores
Canais de Cloreto/metabolismo
Cloretos/metabolismo
Retículo Endoplasmático/ultraestrutura
Feminino
Expressão Gênica
Teste de Complementação Genética
Complexo de Golgi/metabolismo
Complexo de Golgi/ultraestrutura
Seres Humanos
Transporte de Íons
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Nitratos/metabolismo
Oócitos/citologia
Oócitos/efeitos dos fármacos
Oócitos/metabolismo
Técnicas de Patch-Clamp
Multimerização Proteica
Proteínas de Protozoários/antagonistas & inibidores
Proteínas de Protozoários/metabolismo
Saccharomyces cerevisiae/genética
Trypanosoma brucei brucei/crescimento & desenvolvimento
Trypanosoma brucei brucei/ultraestrutura
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CLCN6 protein, human); 0 (CLCN7 protein, human); 0 (Chloride Channels); 0 (Chlorides); 0 (Nitrates); 0 (Protozoan Proteins); Q1O6DSW23R (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188219


  7 / 8062 MEDLINE  
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[PMID]:29188980
[Au] Autor:Partanen J; Isohanni P; Auranen M
[Ti] Título:Myotonia in ion channel diseases of muscle.
[So] Source:Duodecim;132(19):1810-4, 2016.
[Is] ISSN:0012-7183
[Cp] País de publicação:Finland
[La] Idioma:eng
[Ab] Resumo:Ion channel dysfunctions of the muscular cell membrane are usually inheritable, rare diseases. They may become manifest as relatively mild symptoms of muscle stiffness and pain, myotonia or paralysis. We describe two young patients who had an inherited ion channel disease of the muscular cell membrane with mild symptoms. The first patient had a chloride channel dysfunction of the muscular cell membrane, the second one a sodium channel dysfunction. In electromyography findings typical of the respective ion channel disease were detected in both patients. Closer examination of the patients' myotonic sequences occurring in electromyography of the relaxed muscle revealed differences that already enable the evaluation of the type of ion channel disease.
[Mh] Termos MeSH primário: Canais de Cloreto/genética
Miotonia Congênita/diagnóstico
Miotonia Congênita/genética
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Adolescente
Eletromiografia
Seres Humanos
Masculino
Miotonia Congênita/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chloride Channels); 0 (Sodium Channels)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


  8 / 8062 MEDLINE  
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[PMID]:28419445
[Au] Autor:Yang H; Ma L; Wang Y; Zuo W; Li B; Yang Y; Chen Y; Chen L; Wang L; Zhu L
[Ad] Endereço:Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
[Ti] Título:Activation of ClC-3 chloride channel by 17ß-estradiol relies on the estrogen receptor α expression in breast cancer.
[So] Source:J Cell Physiol;233(2):1071-1081, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although extensively studied, the mechanisms by which estrogen promotes breast cancer growth remain to be fully elucidated. Tamoxifen, an antiestrogen agent to treat ERα+ breast cancer, is also a high-affinity blocker of the chloride channels. In this study, we explored the involvement of the chloride channels in the action of estrogen in breast cancer. We found that 17ß-estradiol (17ß-E2) concentration-dependently activated the chloride currents in ERα+ breast cancer MCF-7 cells. Extracellular hypertonic challenge and chloride channel blockers, NPPB and DIDS inhibited the 17ß-E2-activated chloride currents. Decreased the ClC-3 protein expression caused the depletion of the 17ß-E2-activated chloride currents. 17ß-E2-activated chloride currents which relied on the ERα expression were demonstrated by the following evidences. Firstly, 17ß-E2-activated chloride currents could not be observed in ERα- breast cancer MDA-MB-231 cells. Secondly, ER antagonists, tamoxifen and ICI 182,780, and downregulation of ERα expression inhibited or abolished the 17ß-E2-activated chloride currents. Thirdly, ERα expression was induced in MDA-MB-231 cells by ESR1 gene transfection, and then 17ß-E2-activated chloride currents could be observed. In MCF-7 cells, ERα and ClC-3 mainly located in nucleus and translocated to cell plasma and membrane with respect to co-localization following treatment of 17ß-E2. Downregulation of ERα expression could decrease the expression of ClC-3 protein. Conversely, downregulation of ClC-3 expression did not influence the ERα expression. Taken together, our findings demonstrated that ClC-3 is a potential target of 17ß-E2 and is modulated by the ERα in breast cancer cell. Pharmacological modulation of ClC-3 may provide a deep understanding in antiestrogen treatment of breast cancer patients.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Agonistas dos Canais de Cloreto/farmacologia
Canais de Cloreto/efeitos dos fármacos
Estradiol/farmacologia
Receptor alfa de Estrogênio/agonistas
[Mh] Termos MeSH secundário: Neoplasias da Mama/genética
Neoplasias da Mama/patologia
Canais de Cloreto/genética
Canais de Cloreto/metabolismo
Relação Dose-Resposta a Droga
Antagonistas de Estrogênios/farmacologia
Receptor alfa de Estrogênio/genética
Receptor alfa de Estrogênio/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Células MCF-7
Potenciais da Membrana
Interferência de RNA
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chloride Channel Agonists); 0 (Chloride Channels); 0 (ClC-3 channel); 0 (Estrogen Antagonists); 0 (Estrogen Receptor alpha); 0 (estrogen receptor alpha, human); 4TI98Z838E (Estradiol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25963


  9 / 8062 MEDLINE  
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[PMID]:28121009
[Au] Autor:Kamaleddin MA
[Ad] Endereço:Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels.
[So] Source:J Cell Physiol;233(2):787-798, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain.
[Mh] Termos MeSH primário: Canais de Cloreto/efeitos dos fármacos
Canais de Cloreto/metabolismo
Cloretos/metabolismo
Moduladores de Transporte de Membrana/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Asma/tratamento farmacológico
Asma/metabolismo
Cálcio/metabolismo
Canais de Cloreto/química
Canais de Cloreto/genética
Fibrose Cística/tratamento farmacológico
Fibrose Cística/metabolismo
Seres Humanos
Ativação do Canal Iônico/efeitos dos fármacos
Potenciais da Membrana
Neuralgia/tratamento farmacológico
Neuralgia/metabolismo
Conformação Proteica
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Chloride Channels); 0 (Chlorides); 0 (Membrane Transport Modulators); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25823


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[PMID]:29069080
[Au] Autor:Martin NE; Malik S; Calimet N; Changeux JP; Cecchini M
[Ad] Endereço:Laboratoire d'Ingénierie des Fonctions Moléculaire, ISIS, UMR 7006 CNRS, Université de Strasbourg, Strasbourg, France.
[Ti] Título:Un-gating and allosteric modulation of a pentameric ligand-gated ion channel captured by molecular dynamics.
[So] Source:PLoS Comput Biol;13(10):e1005784, 2017 Oct.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pentameric ligand-gated ion channels (pLGICs) mediate intercellular communication at synapses through the opening of an ion pore in response to the binding of a neurotransmitter. Despite the increasing availability of high-resolution structures of pLGICs, a detailed understanding of the functional isomerization from closed to open (gating) and back is currently missing. Here, we provide the first atomistic description of the transition from open to closed (un-gating) in the glutamate-gated chloride channel (GluCl) from Caenorhabditis Elegans. Starting with the active-state structure solved in complex with the neurotransmitter L-glutamate and the positive allosteric modulator (PAM) ivermectin, we analyze the spontaneous relaxation of the channel upon removal of ivermectin by explicit solvent/membrane Molecular Dynamics (MD) simulations. The µs-long trajectories support the conclusion that ion-channel deactivation is mediated by two distinct quaternary transitions, i.e. a global receptor twisting followed by the radial expansion (or blooming) of the extracellular domain. At variance with previous models, we show that pore closing is exclusively regulated by the global twisting, which controls the position of the ß1-ß2 loop relative to the M2-M3 loop at the EC/TM domain interface. Additional simulations with L-glutamate restrained to the crystallographic binding mode and ivermectin removed indicate that the same twisting isomerization is regulated by agonist binding at the orthosteric site. These results provide a structural model for gating in pLGICs and suggest a plausible mechanism for the pharmacological action of PAMs in this neurotransmitter receptor family. The simulated un-gating converges to the X-ray structure of GluCl resting state both globally and locally, demonstrating the predictive character of state-of-art MD simulations.
[Mh] Termos MeSH primário: Regulação Alostérica
Ácido Glutâmico/química
Ativação do Canal Iônico
Ivermectina/química
Ligantes
Simulação de Dinâmica Molecular
[Mh] Termos MeSH secundário: Sítio Alostérico
Sítios de Ligação
Canais de Cloreto/química
Canais de Cloreto/ultraestrutura
Canais Iônicos de Abertura Ativada por Ligante/química
Canais Iônicos de Abertura Ativada por Ligante/ultraestrutura
Modelos Químicos
Neurotransmissores/química
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chloride Channels); 0 (Ligand-Gated Ion Channels); 0 (Ligands); 0 (Neurotransmitter Agents); 0 (glutamate-gated chloride channels); 3KX376GY7L (Glutamic Acid); 70288-86-7 (Ivermectin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171026
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005784



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