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[PMID]:27771553
[Au] Autor:Kato T; Yamamoto T; Nakamura Y; Nanno T; Fukui G; Sufu Y; Hamada Y; Maeda T; Nishimura S; Ishiguchi H; Murakami W; Fukuda M; Xu X; Hino A; Ono M; Oda T; Okuda S; Kobayashi S; Koseki N; Kyushiki H; Yano M
[Ad] Endereço:Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
[Ti] Título:Correction of impaired calmodulin binding to RyR2 as a novel therapy for lethal arrhythmia in the pressure-overloaded heart failure.
[So] Source:Heart Rhythm;14(1):120-127, 2017 01.
[Is] ISSN:1556-3871
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Calmodulin (CaM) is a key modulator of the channel gating function of the ryanodine receptor (RyR). OBJECTIVE: The purpose of this study was to investigate the pathogenic role of RyR-bound CaM in diastolic Ca leakage from the sarcoplasmic reticulum and arrhythmogenesis in pressure-overloaded heart failure. METHODS: Pressure overload was induced in 12-week-old mice by transverse aortic constriction (TAC) using a 27-gauge needle. RESULTS: TAC operation for 8 weeks produced a significant increase in left ventricular end-diastolic diameter and frequent occurrence of lethal arrhythmias after infusion of epinephrine and caffeine in TAC mice. The amount of RyR-bound CaM decreased significantly in TAC mice compared with sham mice. The apparent affinity of CaM binding to RyR decreased in pressure-overloaded cells compared with sham cells and untreated cells. High-affinity calmodulin (HA-CaM; ie, CaM whose binding affinity to RyR was significantly increased) restored a normal level of CaM-RyR binding properties in pressure-overloaded cells. HA-CaM corrected abnormally increased Ca spark frequency in the pressure-overloaded cells to the level seen in the sham cells. The frequency of spontaneous Ca transients in TAC cells during and after 1-5 Hz of field stimulation was 44%, whereas it was significantly attenuated by HA-CaM but not with CaM. CONCLUSION: Several disorders in the RyR channel function characteristic of pressure-overloaded cells (increased spontaneous Ca leakage, delayed afterdepolarization, triggered activity, Ca spark frequency, spontaneous Ca transients) are caused by deteriorated CaM binding to RyR2. These disorders could be rectified by restoring normal CaM binding to RyR2.
[Mh] Termos MeSH primário: Calmodulina/metabolismo
Insuficiência Cardíaca/diagnóstico por imagem
Insuficiência Cardíaca/terapia
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
Taquicardia Ventricular/diagnóstico
[Mh] Termos MeSH secundário: Animais
Mapeamento Potencial de Superfície Corporal/métodos
Canais de Cálcio/metabolismo
Sinalização do Cálcio
Células Cultivadas
Modelos Animais de Doenças
Insuficiência Cardíaca/mortalidade
Camundongos
Camundongos Endogâmicos
Miócitos Cardíacos/metabolismo
Distribuição Aleatória
Valores de Referência
Retículo Sarcoplasmático/metabolismo
Sensibilidade e Especificidade
Taquicardia Ventricular/mortalidade
Taquicardia Ventricular/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Calcium Channels); 0 (Calmodulin); 0 (Ryanodine Receptor Calcium Release Channel)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


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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


  4 / 13173 MEDLINE  
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[PMID]:29227609
[Au] Autor:Nozdrenko DM; Miroshnychenko MS; Soroca VM; Korchins ka LV; Zavodovskiy DO
[Ti] Título:The effect of chlorpyrifos upon ATPase activity of sarcoplasmic reticulum and biomechanics of skeleta l muscle contraction.
[So] Source:Ukr Biochem J;88(2):82-8, 2016 Mar-Apr.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:We investigated the effect of chlorpyrifos, an organophosphate insecticide, on Ca2+,Mg2+-ATPase activity of sarcoplasmic reticulum and on contraction dynamics (force and length changes) of Rana temporaria m. tibialis anterior muscle fiber bundles. All of the used concentrations of chlorpyrifos (10-6 to 10-5 M) caused decrease of Ca2+,Mg2+-ATPase activity. The inhibition of Ca2+,Mg2+-ATPase activity by chlorpyriphos in concentrations of 10-6 M to 7.5·10-6 M is due to permeation of sarcoplasmic reticulum rather than due to direct enzyme inhibition by organophosphate insecticides. The inhibitory properties of the compound were higher at increased concentration and exposure timeframes. Chlorpyrifos in concentration range of 10-6 to 7.5·10-6 M causes changes in muscle fiber response force that were more pronounced than changes in contractile length. We demonstrated inhibition of Ca2+,Mg2+-ATPase activity caused by noncholinergic effects of chlorpyriphos. It is possible to conclude that influence of organophosphate insecticides happens not only in the neuromuscular transmission but also on the level of subcellular structures.
[Mh] Termos MeSH primário: ATPase de Ca(2+) e Mg(2+)/antagonistas & inibidores
Clorpirifos/farmacologia
Inseticidas/farmacologia
Contração Muscular/efeitos dos fármacos
Fibras Musculares Esqueléticas/efeitos dos fármacos
Retículo Sarcoplasmático/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
ATPase de Ca(2+) e Mg(2+)/metabolismo
Cálcio/metabolismo
Relação Dose-Resposta a Droga
Transporte de Íons/efeitos dos fármacos
Contração Muscular/fisiologia
Fibras Musculares Esqueléticas/fisiologia
Rana temporaria
Retículo Sarcoplasmático/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insecticides); EC 3.6.1.- (Ca(2+) Mg(2+)-ATPase); JCS58I644W (Chlorpyrifos); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.02.082


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[PMID]:29227596
[Au] Autor:Veklich TO
[Ti] Título:The inhibitory influence of calix[4]Arene of C-90 on the activity of Ca2+,Mg2+-ATPases in plasma membrane and sarcoplasmic reticulum in myometrium cells.
[So] Source:Ukr Biochem J;88(2):5-15, 2016 Mar-Apr.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:Our study on the plasma membrane vesicles and myometrium cells treated with 0.1% digitonin showed that inhibitory effect of calix[4]arene C-90 (5,11,17,23-tetra(trifluoro)methyl(phenylsulphonylimino)-methylamino- 25,26,27,28-tetrapropoxy-calix[4]arene) on the plasma membrane Ca2+,Mg2+-ATPase was more significant than on the Ca2+,Mg2+-ATPase in sarcoplasmic reticulum (the inhibition coefficient I0.5 values were 20.2 ± 0.5 µM and 57.0 ± 1.4 µM for the plasma membrane Ca2+,Mg2+-ATPase and Ca2+,Mg2+-ATPase in sarcoplasmic reticulum, respectively (n = 5)). Inhibition kinetics of calix[4]arene C-90 effect on the Ca2+,Mg2+- ATPase activities in plasma membrane and sarcoplasmic reticulum were studied. This substance inhibited both pumps as complete noncompetitive inhibitor. Calix[4]arene C-90 caused the increase of intracellular Ca2+ concentration and decrease of hydrodynamic diameter in smooth muscle cells similar to the action of uterotonic drug oxytocin.
[Mh] Termos MeSH primário: ATPase de Ca(2+) e Mg(2+)/antagonistas & inibidores
Calixarenos/farmacologia
Membrana Celular/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Miócitos de Músculo Liso/efeitos dos fármacos
Fenóis/farmacologia
Retículo Sarcoplasmático/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
ATPase de Ca(2+) e Mg(2+)/metabolismo
Cálcio/metabolismo
Membrana Celular/enzimologia
Tamanho Celular
Feminino
Transporte de Íons/efeitos dos fármacos
Cinética
Miócitos de Músculo Liso/enzimologia
Miométrio/efeitos dos fármacos
Miométrio/enzimologia
Ocitocina/farmacologia
Ligação Proteica
Retículo Sarcoplasmático/enzimologia
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Phenols); 0 (calix(4)arene); 130036-26-9 (Calixarenes); 50-56-6 (Oxytocin); EC 3.6.1.- (Ca(2+) Mg(2+)-ATPase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.02.005


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[PMID]:29212003
[Au] Autor:Sztretye M; Geyer N; Vincze J; Al-Gaadi D; Oláh T; Szentesi P; Kis G; Antal M; Balatoni I; Csernoch L; Dienes B
[Ad] Endereço:Department of Physiology, University of Debrecen, Debrecen, Hungary.
[Ti] Título:SOCE Is Important for Maintaining Sarcoplasmic Calcium Content and Release in Skeletal Muscle Fibers.
[So] Source:Biophys J;113(11):2496-2507, 2017 Dec 05.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Store-operated Ca entry (SOCE) is a Ca -entry process activated by the depletion of intracellular stores and has an important role in many cell types. In skeletal muscle, however, its role during physiological muscle activation has been controversial. To address this question, sarcoplasmic reticulum (SR) calcium release in a mouse strain with a naturally occurring mutation in the myostatin gene (Compact (Cmpt)) leading to a hypermuscular yet reduced muscle-force phenotype was compared to that in wild-type mice. To elicit Ca release from the SR of flexor digitorum brevis (FDB) fibers, either a ryanodine receptor agonist (4-chloro-meta-cresol) or depolarizing pulses were used. In muscles from Cmpt mice, endogenous protein levels of STIM1 and Orai1 were reduced, and consequently, SOCE after 4-chloro-meta-cresol-induced store depletion was suppressed. Although the voltage dependence of SR calcium release was not statistically different between wild-type and Cmpt fibers, the amount of releasable calcium was significantly reduced in the latter, indicating a smaller SR content. To assess the immediate role of SOCE in replenishing the SR calcium store, the evolution of intracellular calcium concentration during a train of long-lasting depolarizations to a maximally activating voltage was monitored. Cmpt mice exhibited a faster decline in calcium release, suggesting a compromised ability to refill the SR. A simple model that incorporates a reduced SOCE as an important partner in regulating immediate calcium influx through the surface membrane readily accounts for the steady-state reduction in SR calcium content and its more pronounced decline after calcium release.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Fibras Musculares Esqueléticas/citologia
Retículo Sarcoplasmático/secreção
[Mh] Termos MeSH secundário: Animais
Fenômenos Eletrofisiológicos
Masculino
Camundongos
Fibras Musculares Esqueléticas/fisiologia
Fibras Musculares Esqueléticas/secreção
Mutação
Miostatina/genética
Retículo Sarcoplasmático/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Myostatin); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE


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[PMID]:29025768
[Au] Autor:Sirish P; Ledford HA; Timofeyev V; Thai PN; Ren L; Kim HJ; Park S; Lee JH; Dai G; Moshref M; Sihn CR; Chen WC; Timofeyeva MV; Jian Z; Shimkunas R; Izu LT; Chiamvimonvat N; Chen-Izu Y; Yamoah EN; Zhang XD
[Ad] Endereço:From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biom
[Ti] Título:Action Potential Shortening and Impairment of Cardiac Function by Ablation of .
[So] Source:Circ Arrhythm Electrophysiol;10(10), 2017 Oct.
[Is] ISSN:1941-3084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Intracellular pH (pH ) is critical to cardiac excitation and contraction; uncompensated changes in pH impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl /HCO exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH , but also cardiac excitability. METHODS AND RESULTS: To test the mechanistic role of Slc26a6 in the heart, we took advantage of knockout ( ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of results in action potential shortening. There are reduced Ca transient and sarcoplasmic reticulum Ca load, together with decreased sarcomere shortening in cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH is elevated in cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl /HCO exchange activities of Slc26a6. Moreover, mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. CONCLUSIONS: Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl /HCO transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH , excitability, and contractility. pH is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in mice.
[Mh] Termos MeSH primário: Potenciais de Ação
Antiporters/deficiência
Acoplamento Excitação-Contração
Frequência Cardíaca
Contração Miocárdica
Miócitos Cardíacos/metabolismo
[Mh] Termos MeSH secundário: Animais
Antiporters/genética
Bradicardia/genética
Bradicardia/metabolismo
Bradicardia/fisiopatologia
Células CHO
Cricetulus
Genótipo
Concentração de Íons de Hidrogênio
Cinética
Proteínas de Membrana Transportadoras/genética
Proteínas de Membrana Transportadoras/metabolismo
Camundongos da Linhagem 129
Camundongos Knockout
Fenótipo
Sarcômeros/metabolismo
Retículo Sarcoplasmático/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiporters); 0 (Membrane Transport Proteins); 0 (SLC26A6 protein, human); 0 (Slc26a6 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


  8 / 13173 MEDLINE  
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[PMID]:28916620
[Au] Autor:Hanna AD; Lam A; Thekkedam C; Willemse H; Dulhunty AF; Beard NA
[Ad] Endereço:John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia (A.D.H., A.L., C.T., A.F.D.) and Health Research Institute, Faculty of Education, Science, Technology and Maths, University of Canberra, Australian Capital Territory, Canberra, A
[Ti] Título:The Anthracycline Metabolite Doxorubicinol Abolishes RyR2 Sensitivity to Physiological Changes in Luminal Ca through an Interaction with Calsequestrin.
[So] Source:Mol Pharmacol;92(5):576-587, 2017 Nov.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca binding protein calsequestrin 2 (CSQ2). Normal increases in RyR2 activity in response to increasing diastolic SR [Ca ] are influenced by CSQ2 and are disrupted in arrhythmic conditions. Therefore, we explored the action of doxOL on RyR2's response to changes in luminal [Ca ] seen during diastole. DoxOL abolished the increase in RyR2 activity when luminal Ca was increased from 0.1 to 1.5 mM. This was not due to RyR2 oxidation, but depended entirely on the presence of CSQ2 in the RyR2 complex. DoxOL binding to CSQ2 reduced both the Ca binding capacity of CSQ2 (by 48%-58%) and its aggregation, and lowered CSQ2 association with the RyR2 complex by 67%-77%. Each of these effects on CSQ2, and the lost RyR2 response to changes in luminal [Ca ], was duplicated by exposing native RyR2 channels to subphysiologic (≤1.0 µM) luminal [Ca ]. We suggest that doxOL and low luminal Ca both disrupt the CSQ2 polymer, and that the association of the monomeric protein with the RyR2 complex shifts the increase in RyR2 activity with increasing luminal [Ca ] away from the physiologic [Ca ] range. Subsequently, these changes may render the channel insensitive to changes of luminal Ca that occur through the cardiac cycle. The altered interactions between CSQ2, triadin, and/or junctin and RyR2 may produce an arrhythmogenic substrate in anthracycline-induced cardiotoxicity.
[Mh] Termos MeSH primário: Antraciclinas/metabolismo
Cálcio/metabolismo
Calsequestrina/metabolismo
Doxorrubicina/análogos & derivados
Miócitos Cardíacos/metabolismo
Canal de Liberação de Cálcio do Receptor de Rianodina/fisiologia
[Mh] Termos MeSH secundário: Animais
Antraciclinas/farmacologia
Cálcio/fisiologia
Sinalização do Cálcio/efeitos dos fármacos
Sinalização do Cálcio/fisiologia
Calsequestrina/farmacologia
Técnicas de Cultura de Células/métodos
Relação Dose-Resposta a Droga
Doxorrubicina/metabolismo
Doxorrubicina/farmacologia
Interações Medicamentosas/fisiologia
Miócitos Cardíacos/efeitos dos fármacos
Retículo Sarcoplasmático/efeitos dos fármacos
Retículo Sarcoplasmático/metabolismo
Ovinos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthracyclines); 0 (Calsequestrin); 0 (Ryanodine Receptor Calcium Release Channel); 80168379AG (Doxorubicin); HUH05KI4CF (adriamycinol); SY7Q814VUP (Calcium)
[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:170917
[St] Status:MEDLINE
[do] DOI:10.1124/mol.117.108183


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[PMID]:28863192
[Au] Autor:Tsai CY; Kuo WW; Shibu MA; Lin YM; Liu CN; Chen YH; Day CH; Shen CY; Viswanadha VP; Huang CY
[Ad] Endereço:Department of Pediatrics, China Medical University Beigang Hospital, Yunlin, Taiwan, ROC.
[Ti] Título:E2/ER ß inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca2+-calcineurin signaling.
[So] Source:PLoS One;12(9):e0184153, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17ß-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERß against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERß and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERß also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERß. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERß on ISO-induced Ca2+ influx and hypertrophic effects were totally blocked suggesting that E2/ERß inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca2+ reuptake into sarcoplasmic reticulum through SR Ca2+ cycling modification. In conclusion, E2/ERß suppresses the Ca2+ influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca2+ cycling.
[Mh] Termos MeSH primário: Calcineurina/metabolismo
Cálcio/metabolismo
Cardiomegalia/metabolismo
Receptor beta de Estrogênio/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Inibidores de Calcineurina/farmacologia
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo
Cardiomegalia/induzido quimicamente
Núcleo Celular/metabolismo
Estradiol/metabolismo
Feminino
Isoproterenol/efeitos adversos
Miócitos Cardíacos/metabolismo
Fatores de Transcrição NFATC/metabolismo
Neurônios/metabolismo
Fosforilação
Ratos
Retículo Sarcoplasmático/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcineurin Inhibitors); 0 (Estrogen Receptor beta); 0 (NFATC Transcription Factors); 0 (transcription factor NF-AT c3); 4TI98Z838E (Estradiol); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2); EC 3.1.3.16 (Calcineurin); L628TT009W (Isoproterenol); SY7Q814VUP (Calcium)
[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:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184153


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[PMID]:28859079
[Au] Autor:Colman MA; Pinali C; Trafford AW; Zhang H; Kitmitto A
[Ad] Endereço:School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
[Ti] Título:A computational model of spatio-temporal cardiac intracellular calcium handling with realistic structure and spatial flux distribution from sarcoplasmic reticulum and t-tubule reconstructions.
[So] Source:PLoS Comput Biol;13(8):e1005714, 2017 Aug.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intracellular calcium cycling is a vital component of cardiac excitation-contraction coupling. The key structures responsible for controlling calcium dynamics are the cell membrane (comprising the surface sarcolemma and transverse-tubules), the intracellular calcium store (the sarcoplasmic reticulum), and the co-localisation of these two structures to form dyads within which calcium-induced-calcium-release occurs. The organisation of these structures tightly controls intracellular calcium dynamics. In this study, we present a computational model of intracellular calcium cycling in three-dimensions (3-D), which incorporates high resolution reconstructions of these key regulatory structures, attained through imaging of tissue taken from the sheep left ventricle using serial block face scanning electron microscopy. An approach was developed to model the sarcoplasmic reticulum structure at the whole-cell scale, by reducing its full 3-D structure to a 3-D network of one-dimensional strands. The model reproduces intracellular calcium dynamics during control pacing and reveals the high-resolution 3-D spatial structure of calcium gradients and intracellular fluxes in both the cytoplasm and sarcoplasmic reticulum. We also demonstrated the capability of the model to reproduce potentially pro-arrhythmic dynamics under perturbed conditions, pertaining to calcium-transient alternans and spontaneous release events. Comparison with idealised cell models emphasised the importance of structure in determining calcium gradients and controlling the spatial dynamics associated with calcium-transient alternans, wherein the probabilistic nature of dyad activation and recruitment was constrained. The model was further used to highlight the criticality in calcium spark propagation in relation to inter-dyad distances. The model presented provides a powerful tool for future investigation of structure-function relationships underlying physiological and pathophysiological intracellular calcium handling phenomena at the whole-cell. The approach allows for the first time direct integration of high-resolution images of 3-D intracellular structures with models of calcium cycling, presenting the possibility to directly assess the functional impact of structural remodelling at the cellular scale.
[Mh] Termos MeSH primário: Sinalização do Cálcio/fisiologia
Cálcio/metabolismo
Ventrículos do Coração/citologia
Modelos Cardiovasculares
Retículo Sarcoplasmático/metabolismo
Função Ventricular/fisiologia
[Mh] Termos MeSH secundário: Animais
Simulação por Computador
Seres Humanos
Ovinos
Análise Espaço-Temporal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005714



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