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Pesquisa : A08.675.650.250 [Categoria DeCS]
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  1 / 5596 MEDLINE  
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[PMID]:29214789
[Au] Autor:Kim CW; Han JH; Wu L; Choi JY
[Ad] Endereço:Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, Korea.
[Ti] Título:microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in Zebrafish.
[So] Source:Yonsei Med J;59(1):141-147, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.
[Mh] Termos MeSH primário: Células Ciliadas Auditivas/fisiologia
MicroRNAs/metabolismo
Regeneração/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Contagem de Células
Perfilação da Expressão Gênica
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Proteínas de Fluorescência Verde/metabolismo
Células Ciliadas Auditivas/efeitos dos fármacos
Larva/efeitos dos fármacos
Larva/genética
MicroRNAs/genética
Morfolinos/farmacologia
Neomicina/toxicidade
Regeneração/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN183 microRNA, zebrafish); 0 (MicroRNAs); 0 (Morpholinos); 1404-04-2 (Neomycin); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.141


  2 / 5596 MEDLINE  
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[PMID]:28450830
[Au] Autor:Elliott KL; Kersigo J; Pan N; Jahan I; Fritzsch B
[Ad] Endereço:Department of Biology, University of IowaIowa City, IA, USA.
[Ti] Título:Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation.
[So] Source:Front Neural Circuits;11:25, 2017.
[Is] ISSN:1662-5110
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:We investigate the importance of the degree of peripheral or central target differentiation for mouse auditory afferent navigation to the organ of Corti and auditory nuclei in three different mouse models: first, a mouse in which the differentiation of hair cells, but not central auditory nuclei neurons is compromised ( ); second, a mouse in which hair cell defects are combined with a delayed defect in central auditory nuclei neurons ( ), and third, a mouse in which both hair cells and central auditory nuclei are absent ( ). Our results show that neither differentiated peripheral nor the central target cells of inner ear afferents are needed (hair cells, cochlear nucleus neurons) for segregation of vestibular and cochlear afferents within the hindbrain and some degree of base to apex segregation of cochlear afferents. These data suggest that inner ear spiral ganglion neuron processes may predominantly rely on temporally and spatially distinct molecular cues in the region of the targets rather than interaction with differentiated target cells for a crude topological organization. These developmental data imply that auditory neuron navigation properties may have evolved before auditory nuclei.
[Mh] Termos MeSH primário: Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência
Diferenciação Celular/genética
Células Ciliadas Auditivas/fisiologia
Malformações do Sistema Nervoso/patologia
Fator de Transcrição PAX2/deficiência
Rombencéfalo/patologia
Gânglio Espiral da Cóclea
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Vias Auditivas/embriologia
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Núcleo Coclear/citologia
Núcleo Coclear/embriologia
Núcleo Coclear/crescimento & desenvolvimento
Embrião de Mamíferos
Camundongos
Camundongos Knockout
Malformações do Sistema Nervoso/genética
Fator de Transcrição PAX2/genética
Gânglio Espiral da Cóclea/embriologia
Gânglio Espiral da Cóclea/crescimento & desenvolvimento
Gânglio Espiral da Cóclea/patologia
beta-Galactosidase/genética
beta-Galactosidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Atoh1 protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (PAX2 Transcription Factor); 0 (Pax2 protein, mouse); EC 3.2.1.23 (beta-Galactosidase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.3389/fncir.2017.00025


  3 / 5596 MEDLINE  
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[PMID]:29292089
[Au] Autor:Yu X; Fan Z; Han Y; Zhang D; Xu L; Wang M; Yang Q; Li H; Zhou M; Zhang L; Sun G; Bai X; Li J; Wang H
[Ad] Endereço:Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Otology, Jinan, China; Shandong Institute of Otolaryngology, Jinan, China.
[Ti] Título:Paeoniflorin reduces neomycin-induced ototoxicity in hair cells by suppression of reactive oxygen species generation and extracellularly regulated kinase signalization.
[So] Source:Toxicol Lett;285:9-19, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study was designed to investigate the effect of paeoniflorin (PF) on neomycin-induced ototoxicity in hair cells (HCs). Here, we took advantage of C57BL/6 mice and cochlear explants culture to determine the role of PF in vivo and in vitro. We demonstrated that neomycin exposure induced severe hearing loss and HC damage, which was mediated by activated mitochondrial apoptosis pathway, promoted extracellular signal-regulated kinase (ERK) signaling as well as enhanced reactive oxygen species (ROS) generation in HCs. Interestingly, we found that PF pretreatment significantly alleviated neomycin-induced hearing loss, attenuated HC injury and decreased HC apoptosis caused by neomycin. Mechanistic studies revealed that PF could decrease cellular ROS levels, suppress the activation of ERK signaling and, subsequently, mitigate the imbalance of mitochondrial apoptotic pathway, thus protecting HCs from neomycin-induced apoptosis. This study indicates that PF may serve as an antioxidative and anti-apoptotic agent to prevent hearing loss caused by neomycin.
[Mh] Termos MeSH primário: Antioxidantes/uso terapêutico
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Glucosídeos/uso terapêutico
Células Ciliadas Auditivas/efeitos dos fármacos
Perda Auditiva/prevenção & controle
Monoterpenos/uso terapêutico
Neomicina/toxicidade
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/administração & dosagem
Apoptose/efeitos dos fármacos
Células Cultivadas
Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos
Glucosídeos/administração & dosagem
Células Ciliadas Auditivas/metabolismo
Células Ciliadas Auditivas/patologia
Perda Auditiva/induzido quimicamente
Perda Auditiva/metabolismo
Perda Auditiva/patologia
Camundongos Endogâmicos C57BL
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/patologia
Monoterpenos/administração & dosagem
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Glucosides); 0 (Monoterpenes); 0 (Reactive Oxygen Species); 1404-04-2 (Neomycin); 21AIQ4EV64 (peoniflorin); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE


  4 / 5596 MEDLINE  
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[PMID]:28892484
[Au] Autor:Zhang T; Xu J; Maire P; Xu PX
[Ad] Endereço:Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
[Ti] Título:Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium.
[So] Source:PLoS Genet;13(9):e1006967, 2017 Sep.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The organ of Corti in the cochlea is a two-cell layered epithelium: one cell layer of mechanosensory hair cells that align into one row of inner and three rows of outer hair cells interdigitated with one cell layer of underlying supporting cells along the entire length of the cochlear spiral. These two types of epithelial cells are derived from common precursors in the four- to five-cell layered primordium and acquire functionally important shapes during terminal differentiation through the thinning process and convergent extension. Here, we have examined the role of Six1 in the establishment of the auditory sensory epithelium. Our data show that prior to terminal differentiation of the precursor cells, deletion of Six1 leads to formation of only a few hair cells and defective patterning of the sensory epithelium. Previous studies have suggested that downregulation of Sox2 expression in differentiating hair cells must occur after Atoh1 mRNA activation in order to allow Atoh1 protein accumulation due to antagonistic effects between Atoh1 and Sox2. Our analysis indicates that downregulation of Sox2 in the differentiating hair cells depends on Six1 activity. Furthermore, we found that Six1 is required for the maintenance of Fgf8 expression and dynamic distribution of N-cadherin and E-cadherin in the organ of Corti during differentiation. Together, our analyses uncover essential roles of Six1 in hair cell differentiation and formation of the organ of Corti in the mammalian cochlea.
[Mh] Termos MeSH primário: Diferenciação Celular/genética
Células Ciliadas Auditivas/metabolismo
Proteínas de Homeodomínio/genética
Órgão Espiral/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Animais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Caderinas/genética
Cóclea/crescimento & desenvolvimento
Cóclea/metabolismo
Epitélio/crescimento & desenvolvimento
Epitélio/metabolismo
Fator 8 de Crescimento de Fibroblasto/genética
Regulação da Expressão Gênica no Desenvolvimento
Proteínas de Homeodomínio/biossíntese
Camundongos
Morfogênese/genética
Órgão Espiral/metabolismo
Fatores de Transcrição SOXB1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Atoh1 protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Cadherins); 0 (Fgf8 protein, mouse); 0 (Homeodomain Proteins); 0 (SOXB1 Transcription Factors); 0 (Six1 protein, mouse); 0 (Sox2 protein, mouse); 148997-75-5 (Fibroblast Growth Factor 8)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006967


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[PMID]:28870992
[Au] Autor:Driver EC; Northrop A; Kelley MW
[Ad] Endereço:Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA drivere@nidcd.nih.gov.
[Ti] Título:Cell migration, intercalation and growth regulate mammalian cochlear extension.
[So] Source:Development;144(20):3766-3776, 2017 10 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. We used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling in mouse. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. By contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement and intercalation within the cochlea all require myosin II. These results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea.
[Mh] Termos MeSH primário: Movimento Celular
Cóclea/embriologia
Regulação da Expressão Gênica no Desenvolvimento
[Mh] Termos MeSH secundário: Animais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Padronização Corporal
Proliferação Celular
Tamanho Celular
Feminino
Genótipo
Células Ciliadas Auditivas/citologia
Homozigoto
Mamíferos
Camundongos
Miosina Tipo II/metabolismo
Órgão Espiral/embriologia
Fatores de Transcrição SOXB1/genética
Imagem com Lapso de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Atoh1 protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (SOXB1 Transcription Factors); 0 (Sox2 protein, mouse); EC 3.6.1.- (Myosin Type II)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1242/dev.151761


  6 / 5596 MEDLINE  
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[PMID]:28866362
[Au] Autor:Fritzsch B; Elliott KL
[Ad] Endereço:University of Iowa, Department of Biology, Iowa City, IA 52242, United States. Electronic address: bernd-fritzsch@uiowa.edu.
[Ti] Título:Gene, cell, and organ multiplication drives inner ear evolution.
[So] Source:Dev Biol;431(1):3-15, 2017 11 01.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We review the development and evolution of the ear neurosensory cells, the aggregation of neurosensory cells into an otic placode, the evolution of novel neurosensory structures dedicated to hearing and the evolution of novel nuclei in the brain and their input dedicated to processing those novel auditory stimuli. The evolution of the apparently novel auditory system lies in duplication and diversification of cell fate transcription regulation that allows variation at the cellular level [transforming a single neurosensory cell into a sensory cell connected to its targets by a sensory neuron as well as diversifying hair cells], organ level [duplication of organ development followed by diversification and novel stimulus acquisition] and brain nuclear level [multiplication of transcription factors to regulate various neuron and neuron aggregate fate to transform the spinal cord into the unique hindbrain organization]. Tying cell fate changes driven by bHLH and other transcription factors into cell and organ changes is at the moment tentative as not all relevant factors are known and their gene regulatory network is only rudimentary understood. Future research can use the blueprint proposed here to provide both the deeper molecular evolutionary understanding as well as a more detailed appreciation of developmental networks. This understanding can reveal how an auditory system evolved through transformation of existing cell fate determining networks and thus how neurosensory evolution occurred through molecular changes affecting cell fate decision processes. Appreciating the evolutionary cascade of developmental program changes could allow identifying essential steps needed to restore cells and organs in the future.
[Mh] Termos MeSH primário: Evolução Biológica
Orelha Interna/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Animais
Vias Auditivas/crescimento & desenvolvimento
Vias Auditivas/fisiologia
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia
Orelha Interna/anatomia & histologia
Orelha Interna/fisiologia
Evolução Molecular
Duplicação Gênica
Células Ciliadas Auditivas/citologia
Células Ciliadas Auditivas/fisiologia
Audição/genética
Audição/fisiologia
Mecanorreceptores/citologia
Mecanorreceptores/fisiologia
Modelos Biológicos
Células Receptoras Sensoriais/citologia
Células Receptoras Sensoriais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


  7 / 5596 MEDLINE  
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[PMID]:28837644
[Au] Autor:Yang T; Kersigo J; Wu S; Fritzsch B; Bassuk AG
[Ad] Endereço:Department of Biology, University of Iowa, Iowa City, Iowa, United States of America.
[Ti] Título:Prickle1 regulates neurite outgrowth of apical spiral ganglion neurons but not hair cell polarity in the murine cochlea.
[So] Source:PLoS One;12(8):e0183773, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC. A follow-up study found no PCP polarity defects after loss of Prickle1 (Prickle1-/-) in the cochlea. We show here strong Prickle1 mRNA expression in the spiral ganglion by in situ hybridization and ß-Gal staining, and weak expression in the OC by ß-Gal staining. Consistent with this limited expression in the OC, cochlear HC PCP is unaffected in either Prickle1C251X/C251X mice or Prickle1f/f; Pax2-cre conditional null mice. Meanwhile, type II afferents of apical spiral ganglion neurons (SGN) innervating outer hair cells (OHC) have unusual neurite growth. In addition, afferents from the apex show unusual collaterals in the cochlear nuclei that overlap with basal turn afferents. Our findings argue against the role of Prickle1 in regulating hair cell polarity in the cochlea. Instead, Prickle1 regulates the polarity-related growth of distal and central processes of apical SGNs.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/fisiologia
Polaridade Celular/fisiologia
Cóclea/citologia
Células Ciliadas Auditivas/citologia
Proteínas com Domínio LIM/fisiologia
Neuritos
Neurônios/citologia
Gânglio Espiral da Cóclea/citologia
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Microscopia Eletrônica de Varredura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (LIM Domain Proteins); 0 (Prickle1 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183773


  8 / 5596 MEDLINE  
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[PMID]:28767685
[Au] Autor:Takano K; Kakuki T; Kaneko Y; Kohno T; Kikuchi S; Himi T; Kojima T
[Ad] Endereço:Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
[Ti] Título:Histone deacetylase inhibition prevents cell death induced by loss of tricellular tight junction proteins in temperature-sensitive mouse cochlear cells.
[So] Source:PLoS One;12(8):e0182291, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tricellular tight junctions (tTJs) are specialized structures that occur where the corners of three cells meet to seal adjacent intercellular space. The molecular components of tTJs include tricellulin (TRIC) and lipolysis-stimulated lipoprotein receptor (LSR) which recruits TRIC, are required for normal hearing. Although loss of TRIC causes hearing loss with degeneration of cochlear cells, the detailed mechanisms remains unclear. In the present study, by using temperature-sensitive mouse cochlear cells, US/VOT-E36 cell line, we investigated the changes of TRIC and LSR during cochlear cell differentiation and the effects of histone deacetylase (HDAC) inhibitors against cell degeneration induced by loss of TRIC and LSR. During cell differentiation induced by the temperature change, expression of TRIC and LSR were clearly induced. Treatment with metformin enhanced expression TRIC and LSR via AMPK during cell differentiation. Loss of TRIC and LSR by the siRNAs induced cell death in differentiated cells. Treatment with HDAC inhibitors trichostatin A and HDAC6 inhibitor prevented the cell death induced by loss of TRIC and LSR. Collectively, these findings suggest that both tTJ proteins TRIC and LSR have crucial roles for the differentiated cochlear cell survival, and that HDAC inhibitors may be potential therapeutic agents to prevent hearing loss.
[Mh] Termos MeSH primário: Células Ciliadas Auditivas/citologia
Inibidores de Histona Desacetilases/farmacologia
Proteína 2 com Domínio MARVEL/metabolismo
Metformina/farmacologia
Receptores de Lipoproteínas/metabolismo
[Mh] Termos MeSH secundário: Animais
Morte Celular/efeitos dos fármacos
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular
Regulação da Expressão Gênica/efeitos dos fármacos
Células Ciliadas Auditivas/efeitos dos fármacos
Camundongos
Temperatura Ambiente
Proteínas de Junções Íntimas/metabolismo
Junções Íntimas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histone Deacetylase Inhibitors); 0 (MARVEL Domain Containing 2 Protein); 0 (Marveld2 protein, mouse); 0 (Receptors, Lipoprotein); 0 (Tight Junction Proteins); 0 (angulin-1 protein, mouse); 9100L32L2N (Metformin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182291


  9 / 5596 MEDLINE  
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[PMID]:28729444
[Au] Autor:Xie WR; Jen HI; Seymour ML; Yeh SY; Pereira FA; Groves AK; Klisch TJ; Zoghbi HY
[Ad] Endereço:Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030.
[Ti] Título:An Atoh1-S193A Phospho-Mutant Allele Causes Hearing Deficits and Motor Impairment.
[So] Source:J Neurosci;37(36):8583-8594, 2017 09 06.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Atonal homolog 1 (Atoh1) is a basic helix-loop-helix (bHLH) transcription factor that is essential for the genesis, survival, and maturation of a variety of neuronal and non-neuronal cell populations, including those involved in proprioception, interoception, balance, respiration, and hearing. Such diverse functions require fine regulation at the transcriptional and protein levels. Here, we show that serine 193 (S193) is phosphorylated in Atoh1's bHLH domain Knock-in mice of both sexes bearing a GFP-tagged phospho-dead S193A allele on a null background ( ) exhibit mild cerebellar foliation defects, motor impairments, partial pontine nucleus migration defects, cochlear hair cell degeneration, and profound hearing loss. We also found that heterozygous mice of both sexes ( ) have adult-onset deafness. These data indicate that different cell types have different degrees of vulnerability to loss of Atoh1 function and that hypomorphic alleles should be considered in human hearing loss. The discovery that Atonal homolog 1 (Atoh1) governs the development of the sensory hair cells in the inner ear led to therapeutic efforts to restore these cells in cases of human deafness. Because prior studies of -heterozygous mice did not examine or report on hearing loss in mature animals, it has not been clinical practice to sequence in people with deafness. Here, in seeking to understand how phosphorylation of Atoh1 modulates its effects , we discovered that inner ear hair cells are much more vulnerable to loss of Atoh1 function than other Atoh1-positive cell types and that heterozygous mice actually develop hearing loss late in life. This opens up the possibility that missense mutations in could increase human vulnerability to loss of hair cells because of aging or trauma.
[Mh] Termos MeSH primário: Envelhecimento/genética
Alelos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Predisposição Genética para Doença/genética
Células Ciliadas Auditivas/patologia
Perda Auditiva/genética
Transtornos dos Movimentos/genética
[Mh] Termos MeSH secundário: Envelhecimento/patologia
Animais
Feminino
Técnicas de Introdução de Genes
Perda Auditiva/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Transtornos dos Movimentos/patologia
Mutação de Sentido Incorreto/genética
Serina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Atoh1 protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 452VLY9402 (Serine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0295-17.2017


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Texto completo
[PMID]:28687841
[Au] Autor:Lyon J
[Ti] Título:Hearing Restoration: A Step Closer?
[So] Source:JAMA;318(4):319-320, 2017 Jul 25.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Células Ciliadas Auditivas/fisiologia
Perda Auditiva Provocada por Ruído/terapia
Audição
Regeneração
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Receptores Acoplados a Proteínas-G/fisiologia
Células-Tronco
[Pt] Tipo de publicação:NEWS
[Nm] Nome de substância:
0 (LGR5 protein, human); 0 (Receptors, G-Protein-Coupled)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170709
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.5820



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