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Pesquisa : D08.811.277.040.025.314.250.500 [Categoria DeCS]
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[PMID]:29179218
[Au] Autor:Wang L; Cui Y; Liu Q; Song Y; Hu Q; Tang M; Hescheler J; Xi J
[Ad] Endereço:Department of Physiology and Chinese-German Stem Cell Center, School of Basic Medicine, Huazhong University of Science and Technology, The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
[Ti] Título:Puerarin Enhances Ca2+ Reuptake and Ca2+ Content of Sarcoplasmic Reticulum in Murine Embryonic Stem Cell-Derived Cardiomyocytes via Upregulation of SERCA2a.
[So] Source:Cell Physiol Biochem;44(3):1199-1212, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR. The mRNA expression levels of SR-related genes were examined by quantitative PCR. The protein expression of sarcoplasmic reticulum calcium-ATPase 2a (SERCA2a) was evaluated by immunofluorescent and western blot. RESULTS: Long-term application of puerarin promotes basic properties of spontaneous calcium transient with increased amplitude, decay velocity, and decreased duration. Puerarin fails to alter ICa,L but increases the Ca2+ content of SR. Puerarin-treated ES-CMs have intact SR Ca2+ cycling with more SR Ca2+ reuptake. Long-term application of puerarin asynchronously upregulates the mRNA and protein expression of SERCA2a, as well as the transcripts of calsequestrin and triadin in developing ES-CMs. Application of puerarin during the stage of post-cardiac differentiation upregulates dose-dependently the transcripts of SERCA2a, phospholamban and tridin which can be reversed by the inhibitors of the PI3K/Akt and MAPK/ERK signaling pathways, but shows no effect on the protein expression of SERCA2a. CONCLUSION: This study demonstrates that long-term puerarin treatment enhances Ca2+ reuptake and Ca2+ content via upregulation of SERCA2a.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Isoflavonas/farmacologia
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Regulação para Cima/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Androstadienos/farmacologia
Animais
Benzamidas/farmacologia
Proteínas de Ligação ao Cálcio/metabolismo
Calsequestrina/genética
Calsequestrina/metabolismo
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Diferenciação Celular/efeitos dos fármacos
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Camundongos
Microscopia Confocal
Células-Tronco Embrionárias Murinas/citologia
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Técnicas de Patch-Clamp
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Retículo Sarcoplasmático/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Benzamides); 0 (Calcium-Binding Proteins); 0 (Calsequestrin); 0 (Carrier Proteins); 0 (Isoflavones); 0 (Muscle Proteins); 0 (PD 0325901); 0 (Vasodilator Agents); 0 (phospholamban); 0 (triadin); 67526-95-8 (Thapsigargin); 9N3CBB0BIQ (Diphenylamine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); SY7Q814VUP (Calcium); XVA4O219QW (wortmannin); Z9W8997416 (puerarin)
[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:10.1159/000485450


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[PMID]:29179202
[Au] Autor:Gong LC; Xu HM; Guo GL; Zhang T; Shi JW; Chang C
[Ad] Endereço:Department of Cardiovascular Internal Medicine, Changchun, China.
[Ti] Título:Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139.
[So] Source:Cell Physiol Biochem;44(3):857-869, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. METHODS: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. RESULTS: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. CONCLUSION: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.
[Mh] Termos MeSH primário: Hipóxia Celular
MicroRNAs/metabolismo
RNA Longo não Codificante/metabolismo
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Antagomirs/metabolismo
Apoptose
Sequência de Bases
Linhagem Celular
Movimento Celular
Sobrevivência Celular
Seres Humanos
MicroRNAs/antagonistas & inibidores
MicroRNAs/genética
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Interferência de RNA
RNA Longo não Codificante/antagonistas & inibidores
RNA Longo não Codificante/genética
RNA Interferente Pequeno/metabolismo
Ratos
Reação em Cadeia da Polimerase em Tempo Real
Fatores de Transcrição SOXE/antagonistas & inibidores
Fatores de Transcrição SOXE/genética
Fatores de Transcrição SOXE/metabolismo
Retículo Sarcoplasmático/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Alinhamento de Sequência
Transdução de Sinais
Serina-Treonina Quinases TOR/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Antagomirs); 0 (H19 long non-coding RNA); 0 (MIRN139 microRNA, rat); 0 (MicroRNAs); 0 (RNA, Long Noncoding); 0 (RNA, Small Interfering); 0 (SOXE Transcription Factors); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[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:10.1159/000485354


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[PMID]:27776889
[Au] Autor:Dahl R
[Ad] Endereço:Neurodon LLC, 5700 Tanager St., Schererville, IN 46375, USA. Electronic address: rdahl@neurodon.net.
[Ti] Título:A new target for Parkinson's disease: Small molecule SERCA activator CDN1163 ameliorates dyskinesia in 6-OHDA-lesioned rats.
[So] Source:Bioorg Med Chem;25(1):53-57, 2017 01 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Endoplasmic reticulum (ER) stress is intimately linked to Parkinson's disease (PD) pathophysiology. Disrupted intracellular calcium homeostasis is a major cause of the ER stress seen in dopaminergic neurons, leading to the cell death and subsequent loss of movement and coordination in patients. Dysfunctional calcium handling proteins play a major role in the promulgation of ER stress in PD. Specifically, compromised sarco/endoplasmic reticulum Ca -ATPase (SERCA) has been identified as a major cause of ER stress and neuron loss in PD. We have identified a small molecule activator of SERCA that increases ER calcium content, rescues neurons from ER stress-induced cell death in vitro, and shows significant efficacy in the rat 6-hydroxydopamine (6-OHDA) model of PD. Together, these results support targeting SERCA activation as a viable strategy to develop disease-modifying therapeutics for PD.
[Mh] Termos MeSH primário: Aminoquinolinas/uso terapêutico
Benzamidas/uso terapêutico
Discinesias/tratamento farmacológico
Ativadores de Enzimas/uso terapêutico
Oxidopamina
Doença de Parkinson Secundária/tratamento farmacológico
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Morte Celular/efeitos dos fármacos
Descoberta de Drogas
Discinesias/complicações
Discinesias/metabolismo
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Masculino
Doença de Parkinson Secundária/complicações
Doença de Parkinson Secundária/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoquinolines); 0 (Benzamides); 0 (CDN1163); 0 (Enzyme Activators); 8HW4YBZ748 (Oxidopamine); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171207
[Lr] Data última revisão:
171207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29028823
[Au] Autor:Leong IUS; Stuckey A; Ahanian T; Cederlöf M; Wikstrom JD
[Ad] Endereço:Dermatology and Venereology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
[Ti] Título:Novel mutations in Darier disease and association to self-reported disease severity.
[So] Source:PLoS One;12(10):e0186356, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Darier disease is a rare and severe autosomal dominant skin disease characterised by malodorous keratotic papules in seborrheic areas of the skin. Darier disease affects up to 1 in 30 000 people and is caused by mutations in the ATP2A2 gene, which encodes to the sarco/endoplasmic reticulum calcium-ATPase isoform 2 that pumps calcium into the endoplasmic reticulum. Although many ATP2A2 variants have been described, it is not known if genotype correlates with phenotype, which could be important for prognosis and treatment. This is the first study to use whole exome sequencing to screen the ATP2A2 gene in a cohort of 28 clinically diagnosed Darier disease patients. Twenty-one different disease causing variants were identified and 15 of these were novel. Sixteen of the 21 variants were predicted to be pathogenic using in silico prediction programs. There were seven missense, four intronic/splice-sites, three frameshifts, two in-frame deletions, four nonsense and one synonymous mutations. This study also found ten patients who harbour more than one ATP2A2 variant. The phenotype of the patient cohort was assessed by photography and by patient questionnaires. The genotype-phenotype association was examined for all variants in relation to the patient's disease severity score, and no correlation could be established.
[Mh] Termos MeSH primário: Doença de Darier/genética
Mutação
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
Autorrelato
Índice de Gravidade de Doença
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
Efeito de Coortes
Feminino
Genótipo
Seres Humanos
Masculino
Meia-Idade
Fenótipo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.3.8 (ATP2A2 protein, human); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186356


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[PMID]:28986259
[Au] Autor:Paul M; Kemparaju K; Girish KS
[Ad] Endereço:DOS in Biochemistry, University of Mysore, Manasagangothri, Mysuru 570 006, India.
[Ti] Título:Inhibition of constitutive NF-κB activity induces platelet apoptosis via ER stress.
[So] Source:Biochem Biophys Res Commun;493(4):1471-1477, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Platelets are anucleate cells, known for their pivotal roles in hemostasis, inflammation, immunity, and disease progression. Being anuclear, platelets are known to express several transcriptional factors which exert nongenomic functions, including the positive and negative regulation of platelet activation. NF-κB is one such transcriptional factor involved in the regulation of genes for survival, proliferation, inflammation and immunity. Although, the role NF-κB in platelet activation and aggregation is partially known, its function in management of platelet survival and apoptosis remain unexplored. Therefore, two unrelated inhibitors of NF-κB activation, BAY 11-7082 and MLN4924 were used to determine the role of NF-κB in platelets. Inhibition of NF-κB caused decreased SERCA activity and increased cytosolic Ca level causing ER stress which was determined by the phosphorylation of eIF2-α. Further, there was increased BAX and decreased BCl-2 levels, incidence of mitochondrial membrane potential depolarization, release of cytochrome c into cytosol, caspase activation, PS externalization and cell death in BAY 11-7082 and MLN4924 treated platelets. The obtained results demonstrate the critical role played by NF-κB in Ca homeostasis and survival of platelets. In addition, the study demonstrates the potential side effects associated with NF-κB inhibitors employed during inflammation and cancer therapy.
[Mh] Termos MeSH primário: Apoptose/fisiologia
Plaquetas/citologia
Plaquetas/metabolismo
Estresse do Retículo Endoplasmático/fisiologia
NF-kappa B/antagonistas & inibidores
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Plaquetas/efeitos dos fármacos
Cálcio/sangue
Ciclopentanos/farmacologia
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
NF-kappa B/sangue
Nitrilos/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/sangue
Pirimidinas/farmacologia
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/sangue
Sulfonas/farmacologia
Proteína X Associada a bcl-2/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-(4-methylphenylsulfonyl)-2-propenenitrile); 0 (BAX protein, human); 0 (Cyclopentanes); 0 (NF-kappa B); 0 (Nitriles); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Pyrimidines); 0 (Sulfones); 0 (bcl-2-Associated X Protein); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); S3AZD8D215 (pevonedistat); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE


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[PMID]:28890335
[Au] Autor:Zhao YG; Chen Y; Miao G; Zhao H; Qu W; Li D; Wang Z; Liu N; Li L; Chen S; Liu P; Feng D; Zhang H
[Ad] Endereço:National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
[Ti] Título:The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation.
[So] Source:Mol Cell;67(6):974-989.e6, 2017 Sep 21.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During autophagosome formation in mammalian cells, isolation membranes (IMs; autophagosome precursors) dynamically contact the ER. Here, we demonstrated that the ER-localized metazoan-specific autophagy protein EPG-3/VMP1 controls ER-IM contacts. Loss of VMP1 causes stable association of IMs with the ER, thus blocking autophagosome formation. Interaction of WIPI2 with the ULK1/FIP200 complex and PI(3)P contributes to the formation of ER-IM contacts, and these interactions are enhanced by VMP1 depletion. VMP1 controls contact formation by promoting SERCA (sarco[endo]plasmic reticulum calcium ATPase) activity. VMP1 interacts with SERCA and prevents formation of the SERCA/PLN/SLN inhibitory complex. VMP1 also modulates ER contacts with lipid droplets, mitochondria, and endosomes. These ER contacts are greatly elevated by the SERCA inhibitor thapsigargin. Calmodulin acts as a sensor/effector to modulate the ER contacts mediated by VMP1/SERCA. Our study provides mechanistic insights into the establishment and disassociation of ER-IM contacts and reveals that VMP1 modulates SERCA activity to control ER contacts.
[Mh] Termos MeSH primário: Autofagossomos/enzimologia
Retículo Endoplasmático/enzimologia
Membranas Intracelulares/enzimologia
Proteínas de Membrana/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo
Células COS
Sistemas CRISPR-Cas
Caenorhabditis elegans/enzimologia
Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Proteínas de Ligação ao Cálcio/metabolismo
Cercopithecus aethiops
Genótipo
Células HEK293
Células HeLa
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Gotículas Lipídicas/metabolismo
Proteínas de Membrana/genética
Proteínas Musculares/metabolismo
Fenótipo
Fosfatos de Fosfatidilinositol/metabolismo
Proteolipídeos/metabolismo
Interferência de RNA
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Calcium-Binding Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (Membrane Proteins); 0 (Muscle Proteins); 0 (Phosphatidylinositol Phosphates); 0 (Proteolipids); 0 (Rb1cc1 protein, mouse); 0 (VMP1 protein, human); 0 (VMP1 protein, mouse); 0 (phosphatidylinositol 3-phosphate); 0 (phospholamban); 145018-73-1 (sarcolipin); EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog); EC 2.7.11.1 (Ulk1 protein, mouse); EC 3.6.3.8 (ATP2A2 protein, human); EC 3.6.3.8 (Atp2a2 protein, mouse); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


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[PMID]:28874462
[Au] Autor:McCrink KA; Maning J; Vu A; Jafferjee M; Marrero C; Brill A; Bathgate-Siryk A; Dabul S; Koch WJ; Lymperopoulos A
[Ad] Endereço:From the Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL (K.A.M., J.M., A.V., M.J., C.M., A.B., A.B.-S., S.D., A.L.); and Department of Pharmacology, Center for Translat
[Ti] Título:ß-Arrestin2 Improves Post-Myocardial Infarction Heart Failure via Sarco(endo)plasmic Reticulum Ca -ATPase-Dependent Positive Inotropy in Cardiomyocytes.
[So] Source:Hypertension;70(5):972-981, 2017 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins ßarr (ß-arrestin)-1 and ßarr-2 are functionally distinct in the heart. ßarr1 is cardiotoxic, decreasing contractility by opposing ß AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, ßarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood. Herein, we sought to investigate whether ßarr2 actually increases cardiac contractility. Via proteomic investigations in transgenic mouse hearts and in H9c2 rat cardiomyocytes, we have uncovered that ßarr2 directly interacts with SERCA2a (sarco[endo]plasmic reticulum Ca -ATPase) in vivo and in vitro in a ß AR-dependent manner. This interaction causes acute SERCA2a SUMO (small ubiquitin-like modifier)-ylation, increasing SERCA2a activity and thus, cardiac contractility. ßarr1 lacks this effect. Moreover, ßarr2 does not desensitize ß AR cAMP-dependent procontractile signaling in cardiomyocytes, again contrary to ßarr1. In vivo, post-MI heart failure mice overexpressing cardiac ßarr2 have markedly improved cardiac function, apoptosis, inflammation, and adverse remodeling markers, as well as increased SERCA2a SUMOylation, levels, and activity, compared with control animals. Notably, ßarr2 is capable of ameliorating cardiac function and remodeling post-MI despite not increasing cardiac ßAR number or cAMP levels in vivo. In conclusion, enhancement of cardiac ßarr2 levels/signaling via cardiac-specific gene transfer augments cardiac function safely, that is, while attenuating post-MI remodeling. Thus, cardiac ßarr2 gene transfer might be a novel, safe positive inotropic therapy for both acute and chronic post-MI heart failure.
[Mh] Termos MeSH primário: Cardiotônicos
Insuficiência Cardíaca
Contração Miocárdica
Infarto do Miocárdio
Miócitos Cardíacos
Remodelação Ventricular
beta-Arrestina 2
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/fisiologia
Cardiotônicos/metabolismo
Cardiotônicos/farmacologia
Células Cultivadas
Modelos Animais de Doenças
Técnicas de Transferência de Genes
Insuficiência Cardíaca/etiologia
Insuficiência Cardíaca/metabolismo
Insuficiência Cardíaca/prevenção & controle
Seres Humanos
Camundongos
Contração Miocárdica/efeitos dos fármacos
Contração Miocárdica/fisiologia
Infarto do Miocárdio/complicações
Infarto do Miocárdio/metabolismo
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/fisiologia
Ratos
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Transdução de Sinais
Volume Sistólico
Remodelação Ventricular/efeitos dos fármacos
Remodelação Ventricular/fisiologia
beta-Arrestina 2/metabolismo
beta-Arrestina 2/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiotonic Agents); 0 (beta-Arrestin 2); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.09817


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[PMID]:28855109
[Au] Autor:Li H; Kim HW; Shin SE; Seo MS; An JR; Ha KS; Han ET; Hong SH; Firth AL; Choi IW; Han IY; Lee DS; Yim MJ; Park WS
[Ad] Endereço:Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea.
[Ti] Título:The vasorelaxant effect of mitiglinide via activation of voltage-dependent K channels and SERCA pump in aortic smooth muscle.
[So] Source:Life Sci;188:1-9, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca -activated K (BK ) channel blocker paxilline, inwardly rectifying K (Kir) channel blocker Ba , and ATP-sensitive K (K ) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide. However, application of the voltage-dependent K (Kv) channel blocker 4-AP, effectively inhibited mitiglinide-induced vasorelaxation. Although pretreatment with the Ca channel blocker nifedipine did not alter the mitiglinide-induced vasorelaxation, pretreatment with the sarcoplasmic/endoplasmic reticulum Ca -ATPase (SERCA) pump inhibitor thapsigargin and cyclopiazonic acid reduced the vasorelaxant effect of mitiglinide. In addition, the vasorelaxant effect of mitiglinide was not affected by the inhibitors of adenylyl cyclase, protein kinase A, guanylyl cyclase, or protein kinase G. Elimination of the endothelium and inhibition of endothelium-dependent vasorelaxant mechanisms also did not change the vasorelaxant effect of mitiglinide. SIGNIFICANCE: We proposed that mitiglinide induces vasorelaxation via activation of Kv channels and SERCA pump. However, the vasorelaxant effects of mitiglinide did not involve other K channels, Ca channels, PKA/PKG signaling pathways, or the endothelium.
[Mh] Termos MeSH primário: Aorta Torácica/fisiologia
Isoindóis/farmacologia
Músculo Liso/fisiologia
Canais de Potássio de Abertura Dependente da Tensão da Membrana/agonistas
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/fisiologia
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: 4-Aminopiridina/farmacologia
Adenina/análogos & derivados
Adenina/farmacologia
Animais
Aorta Torácica/efeitos dos fármacos
Bário/farmacologia
Carbazóis/farmacologia
Relação Dose-Resposta a Droga
Interações Medicamentosas
Endotélio Vascular/efeitos dos fármacos
Glibureto/farmacologia
Indóis/farmacologia
Isoindóis/antagonistas & inibidores
Masculino
Músculo Liso/efeitos dos fármacos
Nifedipino/farmacologia
Oxidiazóis/farmacologia
Fenilefrina/farmacologia
Pirróis/farmacologia
Quinoxalinas/farmacologia
Coelhos
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
Vasodilatadores/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one); 0 (Carbazoles); 0 (Indoles); 0 (Isoindoles); 0 (Oxadiazoles); 0 (Potassium Channels, Voltage-Gated); 0 (Pyrroles); 0 (Quinoxalines); 0 (Vasodilator Agents); 126643-37-6 (KT 5823); 17318-31-9 (9-(tetrahydro-2-furyl)-adenine); 1WS297W6MV (Phenylephrine); 24GP945V5T (Barium); 3T9U9Z96L7 (paxilline); 58HV29I28S (KT 5720); 67526-95-8 (Thapsigargin); BH3B64OKL9 (4-Aminopyridine); D86I0XLB13 (mitiglinide); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); I9ZF7L6G2L (Nifedipine); JAC85A2161 (Adenine); SX6K58TVWC (Glyburide); X9TLY4580Z (cyclopiazonic acid)
[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:170901
[St] Status:MEDLINE


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[PMID]:28822538
[Au] Autor:Tong X; Hou X; Wason C; Kopel T; Cohen RA; Dember LM
[Ad] Endereço:Innovative Drug Research Centre, Chongqing University, Chongqing, China; Vascular Biology Section, Boston University Medical Center, Boston, Massachusetts. Electronic address: xiaoyongtong@cqu.edu.cn.
[Ti] Título:Smooth Muscle Nitric Oxide Responsiveness and Clinical Maturation of Hemodialysis Arteriovenous Fistulae.
[So] Source:Am J Pathol;187(9):2095-2101, 2017 Sep.
[Is] ISSN:1525-2191
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The arteriovenous fistula is the preferred type of hemodialysis vascular access for patients with end-stage renal disease, but a high proportion of newly created fistulas fail to mature for use. Stenosis caused by neointimal hyperplasia often is present in fistulas with maturation failure, suggesting that local mechanisms controlling vascular smooth muscle cell (SMC) migration and proliferation are important contributors to maturation failure. SMCs cultured from explants of vein tissue obtained at the time of fistula creation from 19 patients with end-stage renal disease were studied to determine whether smooth muscle responsiveness to nitric oxide is associated with fistula maturation outcomes. Nitric oxide-induced inhibition of smooth muscle cell migration, but not proliferation, was greater in cells from patients with subsequent fistula maturation success than from patients with subsequent fistula maturation failure (mean inhibition percentage, 17 versus 5.7, respectively; P = 0.035). Impaired nitric oxide responsiveness was associated with oxidation of the calcium regulatory protein, sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and was reversed by overexpressing SERCA (1.8-fold increase in inhibition, P = 0.0128) or down-regulating Nox4-based NADPH oxidase (2.3-fold increase in inhibition; P = 0.005). Our data suggest that the nitric oxide responsiveness of SMC migration is associated with fistula maturation success and raises the possibility that therapeutic restoration of nitric oxide responsiveness through manipulation of local mediators may prevent fistula maturation failure.
[Mh] Termos MeSH primário: Derivação Arteriovenosa Cirúrgica
Falência Renal Crônica/terapia
Músculo Liso Vascular/metabolismo
Óxido Nítrico/metabolismo
Diálise Renal/métodos
[Mh] Termos MeSH secundário: Idoso
Movimento Celular/fisiologia
Proliferação Celular/fisiologia
Regulação para Baixo
Feminino
Seres Humanos
Falência Renal Crônica/metabolismo
Masculino
Meia-Idade
NADPH Oxidases/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
31C4KY9ESH (Nitric Oxide); EC 1.6.3.- (NADPH Oxidases); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170821
[St] Status:MEDLINE


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[PMID]:28787446
[Au] Autor:Zhao B; Lucas KJ; Saha TT; Ha J; Ling L; Kokoza VA; Roy S; Raikhel AS
[Ad] Endereço:Department of Entomology and Institute for Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America.
[Ti] Título:MicroRNA-275 targets sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA) to control key functions in the mosquito gut.
[So] Source:PLoS Genet;13(8):e1006943, 2017 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The yellow fever mosquito Aedes aegypti is the major vector of arboviruses, causing numerous devastating human diseases, such as dengue and yellow fevers, Chikungunya and Zika. Female mosquitoes need vertebrate blood for egg development, and repeated cycles of blood feeding are tightly linked to pathogen transmission. The mosquito's posterior midgut (gut) is involved in blood digestion and also serves as an entry point for pathogens. Thus, the mosquito gut is an important tissue to investigate. The miRNA aae-miR-275 (miR-275) has been shown to be required for normal blood digestion in the female mosquito; however, the mechanism of its action has remained unknown. Here, we demonstrate that miR-275 directly targets and positively regulates sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase, which is implicated in active transport of Ca2+ from the cytosol to the sarco/endoplasmic reticulum. We utilized a combination of the gut-specific yeast transcription activator protein Gal4/upstream activating sequence (Gal4/UAS) system and miRNA Tough Decoy technology to deplete the endogenous level of miR-275 in guts of transgenic mosquitoes. This gut-specific reduction of miR-275 post blood meal decreased SERCA mRNA and protein levels of the digestive enzyme late trypsin. It also resulted in a significant reduction of gut microbiota. Moreover, the decrease of miR-275 and SERCA correlated with defects in the Notch signaling pathway and assembly of the gut actin cytoskeleton. The adverse phenotypes caused by miR-275 silencing were rescued by injections of miR-275 mimic. Thus, we have discovered that miR-275 directly targets SERCA, and the maintenance of its level is critical for multiple gut functions in mosquitoes.
[Mh] Termos MeSH primário: Aedes/genética
Retículo Endoplasmático/metabolismo
Proteínas de Insetos/metabolismo
MicroRNAs/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
[Mh] Termos MeSH secundário: Aedes/metabolismo
Animais
Cálcio/metabolismo
Feminino
Trato Gastrointestinal/metabolismo
Inativação Gênica
Proteínas de Insetos/genética
MicroRNAs/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insect Proteins); 0 (MicroRNAs); 0 (RNA, Messenger); 0 (microRNA miR-275, Aedes aegypti); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006943



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