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Pesquisa : D12.776.157.125.806.500 [Categoria DeCS]
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[PMID]:29305862
[Au] Autor:Li Y; Lou C; Wang W
[Ad] Endereço:Department of Pediatrics, Huaihe Hospital, Henan University, Kaifeng 475000, China. Electronic address: liyanyanghuaihe@qq.com.
[Ti] Título:STIM1 deficiency protects the liver from ischemia/reperfusion injury in mice.
[So] Source:Biochem Biophys Res Commun;496(2):422-428, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatic ischemia reperfusion (I/R) injury is unavoidable in various clinical conditions. Despite considerable investigation, the underlying molecular mechanism revealing liver I/R injury remains elusive. Stromal interaction molecule 1 (STIM1) plays essential role in regulating the induction of cellular responses to a number of stress conditions, including temperature changes, elevated ROS, and hypoxia. Here, to explore if STIM1 is involved in hepatic injury, wild type (WT) and STIM1-knockout (STIM1 ) mice were subjected to I/R. Our results indicated that the WT mice with hepatic I/R injury showed higher STIM1 expressions from gene and protein levels in liver tissue samples. Similar results were observed in hypoxia-exposed cells in vitro. Significantly, STIM1 attenuated hepatic injury compared to the WT mice after I/R, as evidenced by the improved pathological alterations in liver sections. WT mice subjected to liver I/R showed higher serum alanine aminotransferase (ALT) and aminotransferase (AST) levels, as well as pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, which were significantly reduced by STIM1 . In addition, STIM1 also decreased the liver mRNA levels of pro-inflammatory cytokines in mice after I/R injury. Furthermore, significantly decreased oxidative stress was found in STIM1 mice after I/R injury compared to the WT group of mice, evidenced by the enhanced superoxide dismutase (SOD) activity and the reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels in liver tissue samples. Moreover, STIM1 mice with hepatic I/R injury displayed the down-regulated nuclear factor of activated T cell (NFAT1), Orai1 and cleaved Caspase-3 levels in liver, contributing to apoptosis suppression. The results above were confirmed in hypoxia-treated cells lacking of STIM1 expression. Together, the findings suggested that STIM1-deletion protects the liver from I/R injury in mice through inhibiting inflammation, oxidative stress and apoptosis. STIM1 could be considered as a potential therapeutic target to ameliorate I/R injury.
[Mh] Termos MeSH primário: Macrófagos do Fígado/metabolismo
Fígado/metabolismo
Traumatismo por Reperfusão/genética
Molécula 1 de Interação Estromal/genética
[Mh] Termos MeSH secundário: Alanina Transaminase/sangue
Animais
Apoptose/genética
Aspartato Aminotransferases/sangue
Caspase 3/genética
Caspase 3/metabolismo
Regulação da Expressão Gênica
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Interleucina-6/genética
Interleucina-6/metabolismo
Macrófagos do Fígado/patologia
Fígado/patologia
Masculino
Malondialdeído/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fatores de Transcrição NFATC/genética
Fatores de Transcrição NFATC/metabolismo
Proteína ORAI1/genética
Proteína ORAI1/metabolismo
Estresse Oxidativo
Cultura Primária de Células
Espécies Reativas de Oxigênio/metabolismo
Traumatismo por Reperfusão/metabolismo
Traumatismo por Reperfusão/patologia
Traumatismo por Reperfusão/prevenção & controle
Molécula 1 de Interação Estromal/deficiência
Superóxido Dismutase/genética
Superóxido Dismutase/metabolismo
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (NFATC Transcription Factors); 0 (Nfatc2 protein, mouse); 0 (ORAI1 Protein); 0 (Orai1 protein, mouse); 0 (Reactive Oxygen Species); 0 (Stim1 protein, mouse); 0 (Stromal Interaction Molecule 1); 0 (Tumor Necrosis Factor-alpha); 4Y8F71G49Q (Malondialdehyde); EC 1.15.1.1 (Superoxide Dismutase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 3.4.22.- (Casp3 protein, mouse); EC 3.4.22.- (Caspase 3)
[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:180107
[St] Status:MEDLINE


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[PMID]:29030115
[Au] Autor:Vaeth M; Maus M; Klein-Hessling S; Freinkman E; Yang J; Eckstein M; Cameron S; Turvey SE; Serfling E; Berberich-Siebelt F; Possemato R; Feske S
[Ad] Endereço:Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
[Ti] Título:Store-Operated Ca Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming.
[So] Source:Immunity;47(4):664-679.e6, 2017 Oct 17.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Store-operated Ca entry (SOCE) is the main Ca influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca release-activated Ca (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca -dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation. SOCE directs the metabolic reprogramming of naive T cells by regulating the expression of glucose transporters, glycolytic enzymes, and metabolic regulators through the activation of nuclear factor of activated T cells (NFAT) and the PI3K-AKT kinase-mTOR nutrient-sensing pathway. We propose that SOCE controls a critical "metabolic checkpoint" at which T cells assess adequate nutrient supply to support clonal expansion and adaptive immune responses.
[Mh] Termos MeSH primário: Canais de Cálcio/imunologia
Sinalização do Cálcio/imunologia
Cálcio/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Calcineurina/imunologia
Calcineurina/metabolismo
Cálcio/metabolismo
Canais de Cálcio/metabolismo
Divisão Celular/imunologia
Células Cultivadas
Feminino
Glicólise/imunologia
Células HEK293
Seres Humanos
Immunoblotting
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Microscopia Confocal
Fatores de Transcrição NFATC/genética
Fatores de Transcrição NFATC/imunologia
Fatores de Transcrição NFATC/metabolismo
Fosfatidilinositol 3-Quinases/imunologia
Fosfatidilinositol 3-Quinases/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transdução de Sinais/imunologia
Molécula 1 de Interação Estromal/genética
Molécula 1 de Interação Estromal/imunologia
Molécula 1 de Interação Estromal/metabolismo
Molécula 2 de Interação Estromal/genética
Molécula 2 de Interação Estromal/imunologia
Molécula 2 de Interação Estromal/metabolismo
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (NFATC Transcription Factors); 0 (Stromal Interaction Molecule 1); 0 (Stromal Interaction Molecule 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.1.3.16 (Calcineurin); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171015
[St] Status:MEDLINE


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[PMID]:28935720
[Au] Autor:Terry LE; VerMeer M; Giles J; Tran QK
[Ad] Endereço:Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, U.S.A.
[Ti] Título:Suppression of store-operated Ca entry by activation of GPER: contribution to a clamping effect on endothelial Ca signaling.
[So] Source:Biochem J;474(21):3627-3642, 2017 Oct 23.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The G protein-coupled estrogen receptor 1 (GPER, formerly also known as GPR30) modulates many Ca -dependent activities in endothelial cells. However, the underlying mechanisms are poorly understood. We recently reported that GPER acts to prolong cytoplasmic Ca signals by interacting with and promoting inhibitory phosphorylation of the plasma membrane Ca -ATPase. In the present study, we examined the role of GPER activation in modulating store-operated Ca entry (SOCE) via effects on the stromal interaction molecule 1 (STIM1). GPER activation by agonist G-1 reduces the peak but prolongs the plateau of bradykinin-induced Ca signals in primary endothelial cells. G-1 dose-dependently inhibits thapsigargin-induced SOCE measured by the Mn quenching method. GPER heterologous expression reduces SOCE, which is further pronounced by G-1 treatment. Consistently, GPER gene silencing in endothelial cells is associated with an increase in SOCE. Treatment with G-1 reduces puncta formation by STIM1 triggered by the activation of SOCE. The effect of GPER activation to inhibit SOCE is not affected by combined nonphosphorylatable substitutions at serines 486 and 668 on STIM1, but is substantially reduced by similar substitutions at serines 575, 608 and 621. Taken together with our recently reported inhibitory actions of GPER on Ca efflux, the current data contribute to a model in which GPER acts to clamp agonist-induced cytoplasmic Ca signals. Kinetic modeling based on current and reported data is used to estimate the overall effect of GPER activation on point activity of endothelial nitric oxide synthase during the time course of agonist-induced total Ca signals.
[Mh] Termos MeSH primário: Bradicinina/farmacologia
Ciclopentanos/farmacologia
Células Endoteliais/metabolismo
Modelos Biológicos
Proteínas de Neoplasias/metabolismo
Quinolinas/farmacologia
Molécula 1 de Interação Estromal/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Sinalização do Cálcio
Células Endoteliais/citologia
Células HEK293
Seres Humanos
Mutação de Sentido Incorreto
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Molécula 1 de Interação Estromal/antagonistas & inibidores
Molécula 1 de Interação Estromal/genética
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone); 0 (Cyclopentanes); 0 (Neoplasm Proteins); 0 (Quinolines); 0 (STIM1 protein, human); 0 (Stromal Interaction Molecule 1); S8TIM42R2W (Bradykinin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170630


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[PMID]:28821659
[Au] Autor:Ryu C; Jang DC; Jung D; Kim YG; Shim HG; Ryu HH; Lee YS; Linden DJ; Worley PF; Kim SJ
[Ad] Endereço:Departments of Physiology and.
[Ti] Título:STIM1 Regulates Somatic Ca Signals and Intrinsic Firing Properties of Cerebellar Purkinje Neurons.
[So] Source:J Neurosci;37(37):8876-8894, 2017 Sep 13.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Control of Ca flux between the cytosol and intracellular Ca stores is essential for maintaining normal cellular function. It has been well established in both neuronal and non-neuronal cells that stromal interaction molecule 1 (STIM1) initiates and regulates refilling Ca into the ER. Here, we describe a novel, additional role for STIM1, the regulation of free cytosolic Ca , and the consequent control of spike firing in neurons. Among central neurons, cerebellar Purkinje neurons express the highest level of STIM1, and they fire continuously in the absence of stimulation, making somatic Ca homeostasis of particular importance. By using Purkinje neuron-specific STIM1 knock-out (STIM1 ) male mice, we found that the deletion of STIM1 delayed clearance of cytosolic Ca in the soma during ongoing neuronal firing. Deletion of STIM1 also reduced the Purkinje neuronal excitability and impaired intrinsic plasticity without affecting long-term synaptic plasticity. In vestibulo-ocular reflex learning, STIM1 male mice showed severe deficits in memory consolidation, whereas they were normal in memory acquisition. Our results suggest that STIM1 is critically involved in the regulation of the neuronal excitability and the intrinsic plasticity of the Purkinje neurons as well as cerebellar memory consolidation. Stromal interaction molecule 1 (STIM1), which regulates the refilling of ER Ca , has been investigated in several systems including the CNS. In addition to a previous study showing that STIM1 regulates dendritic ER Ca refilling and mGluR1-mediated synaptic transmission, we provide compelling evidence describing a novel role of STIM1 in spike firing Purkinje neurons. We found that STIM1 regulates cytosolic Ca clearance of the soma during spike firing, and the interruption of this cytosolic Ca clearing disrupts neuronal excitability and cerebellar memory consolidation. Our results provide new insights into neuronal functions of STIM1 from single neuronal Ca dynamics to behavior level.
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Sinalização do Cálcio/fisiologia
Cálcio/metabolismo
Consolidação da Memória/fisiologia
Células de Purkinje/fisiologia
Molécula 1 de Interação Estromal/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Molécula 1 de Interação Estromal/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Stim1 protein, mouse); 0 (Stromal Interaction Molecule 1); SY7Q814VUP (Calcium)
[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:170820
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3973-16.2017


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[PMID]:28732182
[Au] Autor:Furukawa Y; Haruyama N; Nikaido M; Nakanishi M; Ryu N; Oh-Hora M; Kuremoto K; Yoshizaki K; Takano Y; Takahashi I
[Ad] Endereço:1 Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth, and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
[Ti] Título:Stim1 Regulates Enamel Mineralization and Ameloblast Modulation.
[So] Source:J Dent Res;96(12):1422-1429, 2017 Nov.
[Is] ISSN:1544-0591
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Loss-of-function mutations in the Ca release-activated Ca channel genes ORAI1 and STIM1 abolish store-operated Ca entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 ( Stim1 cKO [conditional knockout]), Stim2 ( Stim2 cKO), and Stim1 and Stim2 ( Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control ( Stim1/2 ) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.
[Mh] Termos MeSH primário: Ameloblastos/fisiologia
Amelogênese/genética
Molécula 1 de Interação Estromal/genética
[Mh] Termos MeSH secundário: Amelogênese Imperfeita/genética
Animais
Canais de Cálcio/genética
Proteínas do Esmalte Dentário/genética
Genótipo
Imuno-Histoquímica
Camundongos
Camundongos Transgênicos
Microscopia Eletrônica de Varredura
Fenótipo
Reação em Cadeia da Polimerase
Microtomografia por Raio-X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (Dental Enamel Proteins); 0 (Stromal Interaction Molecule 1); 0 (enamel matrix proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1177/0022034517719872


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[PMID]:28724541
[Au] Autor:Clemens RA; Chong J; Grimes D; Hu Y; Lowell CA
[Ad] Endereço:Department of Pediatrics, University of California, San Francisco, CA.
[Ti] Título:STIM1 and STIM2 cooperatively regulate mouse neutrophil store-operated calcium entry and cytokine production.
[So] Source:Blood;130(13):1565-1577, 2017 Sep 28.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neutrophils are key effector cells of the innate immune system. Calcium-dependent signaling pathways initiated by store-operated calcium entry (SOCE) are known to regulate neutrophil activation; however, the precise mechanism of this process remains unclear. STIM1 and STIM2 are calcium-sensing molecules that link calcium depletion of the endoplasmic reticulum with opening of plasma membrane calcium channels. Although a role for STIM1 in neutrophil SOCE and activation has been established, the function of STIM2 is unknown. Here we use mice with conditional ablation of and/or to investigate the role of STIM2 in neutrophil activation. We demonstrate that loss of STIM2 results in decreased SOCE, particularly at lower doses of agonists. Reactive oxygen species (ROS) production, degranulation, and phagocytosis are normal in the absence of STIM2, suggesting STIM1 is the dominant calcium sensor required for classical short-term neutrophil responses. However, neutrophil cytokine production required STIM2, but not STIM1, at least in part as a result of redox regulation of cytokine gene expression. In vivo loss of STIM2 results in lower cytokine levels and protection from mortality in a mouse model of systemic inflammatory response syndrome. These data, combined with previous studies focusing on STIM1, define distinct but cooperative functions for STIM1 and STIM2 in modulating neutrophil bactericidal and cytokine responses.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Citocinas/biossíntese
Ativação de Neutrófilo
Molécula 1 de Interação Estromal/fisiologia
Molécula 2 de Interação Estromal/fisiologia
[Mh] Termos MeSH secundário: Animais
Canais de Cálcio/metabolismo
Camundongos
Oxirredução
Molécula 1 de Interação Estromal/imunologia
Molécula 2 de Interação Estromal/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (Cytokines); 0 (Stim1 protein, mouse); 0 (Stim2 protein, mouse); 0 (Stromal Interaction Molecule 1); 0 (Stromal Interaction Molecule 2); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-11-751230


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[PMID]:28704809
[Au] Autor:Stagno MJ; Zacharopoulou N; Bochem J; Tsapara A; Pelzl L; Al-Maghout T; Kallergi G; Alkahtani S; Alevizopoulos K; Dimas K; Calogeropoulou T; Warmann SW; Lang F; Schmid E; Stournaras C
[Ad] Endereço:Department of Pediatric Surgery & Pediatric Urology, Children's Hospital, Eberhard-Karls-University Tuebingen, Tuebingen, Germany.
[Ti] Título:Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells.
[So] Source:Cell Physiol Biochem;42(4):1366-1376, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells. METHODS: Migration was assessed by transwell and wound healing assays, Orai1 and Stim1 abundance by RT-PCR and confocal immunofluorescence microscopy, Fura-2 fluorescence was utilized to determine intracellular Ca2+ and Western blotting for FAK/pFAK measurements. RESULTS: We observed strong inhibition of cell migration in istaroxime treated DU-145 prostate cancer cells. Istaroxime further decreased Orai1 and Stim1 transcript levels and downregulated Orai1 protein expression. Moreover, SOCE was significantly decreased upon istaroxime treatment. Furthermore, istaroxime strikingly diminished phosphorylated FAK levels. Interestingly, the efficacy of istaroxime on the inhibition of DU-145 cell migration was further enhanced by blocking Orai1 with 2-APB and FAK with the specific inhibitor PF-00562271. These results provide strong evidence that istaroxime prevents cell migration and motility of DU-145 prostate tumor cells, an effect at least partially attributed to Orai1 downregulation and FAK de-activation. CONCLUSION: Collectively our results indicate that this enzyme inhibitor, besides its pro-apoptotic action, affects motility of cancer cells, supporting its potential role as a strong candidate for further clinical cancer drug development.
[Mh] Termos MeSH primário: Movimento Celular/efeitos dos fármacos
Células Epiteliais/efeitos dos fármacos
Etiocolanolona/análogos & derivados
Quinase 1 de Adesão Focal/genética
Regulação Neoplásica da Expressão Gênica
Proteína ORAI1/genética
Bloqueadores dos Canais de Sódio/farmacologia
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Canais de Cálcio/genética
Canais de Cálcio/metabolismo
Linhagem Celular Tumoral
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Etiocolanolona/farmacologia
Corantes Fluorescentes/química
Quinase 1 de Adesão Focal/antagonistas & inibidores
Quinase 1 de Adesão Focal/metabolismo
Fura-2/química
Seres Humanos
Masculino
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Proteína ORAI1/antagonistas & inibidores
Proteína ORAI1/metabolismo
Fosforilação/efeitos dos fármacos
Próstata/efeitos dos fármacos
Próstata/metabolismo
Próstata/patologia
Inibidores de Proteínas Quinases/farmacologia
Pirimidinas/farmacologia
Transdução de Sinais
Molécula 1 de Interação Estromal/antagonistas & inibidores
Molécula 1 de Interação Estromal/genética
Molécula 1 de Interação Estromal/metabolismo
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (Fluorescent Dyes); 0 (Neoplasm Proteins); 0 (ORAI1 Protein); 0 (ORAI1 protein, human); 0 (PF-00562271); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 0 (STIM1 protein, human); 0 (Sodium Channel Blockers); 0 (Stromal Interaction Molecule 1); 0 (Sulfonamides); 97CGB1M48I (Etiocholanolone); EC 2.7.10.2 (Focal Adhesion Kinase 1); EC 2.7.10.2 (PTK2 protein, human); SY7Q814VUP (Calcium); TSN3DL106G (Fura-2); W8I9H2TPPL (Istaroxime)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1159/000479200


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[PMID]:28624623
[Au] Autor:Huang Q; Cao H; Zhan L; Sun X; Wang G; Li J; Guo X; Ren T; Wang Z; Lyu Y; Liu B; An J; Xing J
[Ad] Endereço:State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
[Ti] Título:Mitochondrial fission forms a positive feedback loop with cytosolic calcium signaling pathway to promote autophagy in hepatocellular carcinoma cells.
[So] Source:Cancer Lett;403:108-118, 2017 Sep 10.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Both mitochondrial morphology and the level of cytosolic calcium [Ca ]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored. Our results showed that mitochondrial fission increased the [Ca ]c and calcium oscillation in HCC cells. We further found that mitochondrial fission-mediated calcium signaling was dependent on ROS-activated NF-κB pathways, which facilitated the expression of STIM1 and subsequent store-operated calciumentry. Additionally, we also demonstrated that increase in [Ca ]c promoted mitochondrial fission by up-regulating expression of Drp1 and FIS1 via transcription factors NFATC2 and c-Myc, respectively. Moreover, the positive feedback loop significantly promoted HCC cell global autophagy by Ca /CAMKK/AMPK pathway. Our data demonstrate a positive feedback loop between mitochondrial fission and cytosolic calcium signaling and their promoting role in autophagy of HCC cells, which provides evidence for this loop as a potential drug target in tumor treatment.
[Mh] Termos MeSH primário: Autofagia
Sinalização do Cálcio
Carcinoma Hepatocelular/metabolismo
Neoplasias Hepáticas/metabolismo
Mitocôndrias Hepáticas/metabolismo
Dinâmica Mitocondrial
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/patologia
Linhagem Celular Tumoral
Retroalimentação Fisiológica
GTP Fosfo-Hidrolases/genética
GTP Fosfo-Hidrolases/metabolismo
Seres Humanos
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/patologia
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Proteínas Associadas aos Microtúbulos/genética
Proteínas Associadas aos Microtúbulos/metabolismo
Mitocôndrias Hepáticas/patologia
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
NF-kappa B/metabolismo
Fatores de Transcrição NFATC/metabolismo
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Proteínas Proto-Oncogênicas c-myc/metabolismo
Interferência de RNA
Espécies Reativas de Oxigênio/metabolismo
Molécula 1 de Interação Estromal/genética
Molécula 1 de Interação Estromal/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FIS1 protein, human); 0 (MYC protein, human); 0 (Membrane Proteins); 0 (Microtubule-Associated Proteins); 0 (Mitochondrial Proteins); 0 (NF-kappa B); 0 (NFATC Transcription Factors); 0 (NFATC2 protein, human); 0 (Neoplasm Proteins); 0 (Proto-Oncogene Proteins c-myc); 0 (Reactive Oxygen Species); 0 (STIM1 protein, human); 0 (Stromal Interaction Molecule 1); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.5.5 (DNM1L protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170619
[St] Status:MEDLINE


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[PMID]:28600435
[Au] Autor:Chen YJ; Chang CL; Lee WR; Liou J
[Ad] Endereço:Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX.
[Ti] Título:RASSF4 controls SOCE and ER-PM junctions through regulation of PI(4,5)P .
[So] Source:J Cell Biol;216(7):2011-2025, 2017 Jul 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RAS association domain family 4 (RASSF4) is involved in tumorigenesis and regulation of the Hippo pathway. In this study, we identify new functional roles of RASSF4. First, we discovered that RASSF4 regulates store-operated Ca entry (SOCE), a fundamental Ca signaling mechanism, by affecting the translocation of the endoplasmic reticulum (ER) Ca sensor stromal interaction molecule 1 (STIM1) to ER-plasma membrane (PM) junctions. It was further revealed that RASSF4 regulates the formation of ER-PM junctions and the ER-PM tethering function of extended synaptotagmins E-Syt2 and E-Syt3. Moreover, steady-state PM phosphatidylinositol 4,5-bisphosphate (PI[4,5]P ) levels, important for localization of STIM1 and E-Syts at ER-PM junctions, were reduced in -knockdown cells. Furthermore, we demonstrated that RASSF4 interacts with and regulates the activity of adenosine diphosphate ribosylation factor 6 (ARF6), a small G protein and upstream regulator of type I phosphatidylinositol phosphate kinases (PIP5Ks) and PM PI(4,5)P levels. Overall, our study suggests that RASSF4 controls SOCE and ER-PM junctions through ARF6-dependent regulation of PM PI(4,5)P levels, pivotal for a variety of physiological processes.
[Mh] Termos MeSH primário: Sinalização do Cálcio
Membrana Celular/metabolismo
Retículo Endoplasmático/metabolismo
Proteínas de Neoplasias/metabolismo
Proteína ORAI1/metabolismo
Fosfatidilinositol 4,5-Difosfato/metabolismo
Molécula 1 de Interação Estromal/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Fatores de Ribosilação do ADP/genética
Fatores de Ribosilação do ADP/metabolismo
Feminino
Células HeLa
Seres Humanos
Microscopia de Fluorescência
Microscopia de Vídeo
Proteínas de Neoplasias/genética
Fosfotransferases (Aceptor do Grupo Álcool)/genética
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
Transporte Proteico
Interferência de RNA
Molécula 1 de Interação Estromal/genética
Sinaptotagmina II/genética
Sinaptotagmina II/metabolismo
Sinaptotagminas/genética
Sinaptotagminas/metabolismo
Fatores de Tempo
Imagem com Lapso de Tempo
Transfecção
Proteínas Supressoras de Tumor/genética
Neoplasias do Colo do Útero/genética
Neoplasias do Colo do Útero/metabolismo
Neoplasias do Colo do Útero/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (ORAI1 Protein); 0 (ORAI1 protein, human); 0 (Phosphatidylinositol 4,5-Diphosphate); 0 (RASSF4 protein, human); 0 (STIM1 protein, human); 0 (SYT2 protein, human); 0 (SYT3 protein, human); 0 (Stromal Interaction Molecule 1); 0 (Synaptotagmin II); 0 (Tumor Suppressor Proteins); 134193-27-4 (Synaptotagmins); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170611
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201606047


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[PMID]:28592415
[Au] Autor:Troupes CD; Wallner M; Borghetti G; Zhang C; Mohsin S; von Lewinski D; Berretta RM; Kubo H; Chen X; Soboloff J; Houser S
[Ad] Endereço:From the Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (C.D.T., M.W., G.B., C.Z., S.M., R.M.B., H.K., X.C., S.H.); Department of Cardiology, Medical University of Graz, Austria (D.v.L.); and Fels Institute for Cancer Research and Molecular Biology
[Ti] Título:Role of STIM1 (Stromal Interaction Molecule 1) in Hypertrophy-Related Contractile Dysfunction.
[So] Source:Circ Res;121(2):125-136, 2017 Jul 07.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Pathological increases in cardiac afterload result in myocyte hypertrophy with changes in myocyte electrical and mechanical phenotype. Remodeling of contractile and signaling Ca occurs in pathological hypertrophy and is central to myocyte remodeling. STIM1 (stromal interaction molecule 1) regulates Ca signaling in many cell types by sensing low endoplasmic reticular Ca levels and then coupling to plasma membrane Orai channels to induce a Ca influx pathway. Previous reports suggest that STIM1 may play a role in cardiac hypertrophy, but its role in electrical and mechanical phenotypic alterations is not well understood. OBJECTIVE: To define the contributions of STIM1-mediated Ca influx on electrical and mechanical properties of normal and diseased myocytes, and to determine whether Orai channels are obligatory partners for STIM1 in these processes using a clinically relevant large animal model of hypertrophy. METHODS AND RESULTS: Cardiac hypertrophy was induced by slow progressive pressure overload in adult cats. Hypertrophied myocytes had increased STIM1 expression and activity, which correlated with altered Ca -handling and action potential (AP) prolongation. Exposure of hypertrophied myocytes to the Orai channel blocker BTP2 caused a reduction of AP duration and reduced diastolic Ca spark rate. BTP2 had no effect on normal myocytes. Forced expression of STIM1 in cultured adult feline ventricular myocytes increased diastolic spark rate and prolonged AP duration. STIM1 expression produced an increase in the amount of Ca stored within the sarcoplasmic reticulum and activated Ca /calmodulin-dependent protein kinase II. STIM1 expression also increased spark rates and induced spontaneous APs. STIM1 effects were eliminated by either BTP2 or by coexpression of a dominant negative Orai construct. CONCLUSIONS: STIM1 can associate with Orai in cardiac myocytes to produce a Ca influx pathway that can prolong the AP duration and load the sarcoplasmic reticulum and likely contributes to the altered electromechanical properties of the hypertrophied heart.
[Mh] Termos MeSH primário: Cardiomegalia/metabolismo
Cardiomegalia/fisiopatologia
Contração Miocárdica/fisiologia
Proteínas de Neoplasias/biossíntese
Molécula 1 de Interação Estromal/biossíntese
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Animais
Gatos
Células Cultivadas
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (STIM1 protein, human); 0 (Stromal Interaction Molecule 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.311094



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