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SERCA OR SERCA2 OR SERCA2a

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https://www.readbyqxmd.com/read/29764938/redistribution-of-serca-calcium-pump-conformers-during-intracellular-calcium-signaling
#1
Olga N Raguimova, Nikolai Smolin, Elisa Bovo, Siddharth Bhayani, Joseph M Autry, Aleksey V Zima, Seth L Robia
The conformational changes of a calcium transport A TPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29761773/-dyskeratosis-follicularis
#2
Inger Lily Dorf, Mette Sommerlund, Ann-Bine Skytte, Uffe Koppelhus
Dyskeratosis follicularis (or Darier's disease) is a genetic skin disease with an autosomal dominant inheritance and a prevalence of 1:100,000-1:35,000. Mutations in the gene ATP2A2 encoding the Ca2+-ATPase SERCA2 in the endoplasmatic reticulum lead to acantholysis and dyskeratosis in the epidermis, nails and mucosal membranes with resultant brown-yellow coloured, often infested skin papules and nail changes. The newly established Danish database for genodermatoses is embarking on an extensive registration of all Danish patients with Darier's disease...
May 7, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29760186/hypertrophic-cardiomyopathy-mutations-increase-myofilament-ca-2-buffering-alter-intracellular-ca-2-handling-and-stimulate-ca-2-dependent-signalling
#3
Paul Robinson, Xing Liu, Alexander Sparrow, Suketu Patel, Yin Hua Zhang, Barbara Casadei, Hugh Watkins, Charles S Redwood
Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca2+ -sensitivity. Mouse models exhibit increased Ca2+ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca2+ - buffering and altered Ca2+ -handling contribute to HCM pathogenesis via activation of Ca2+ -dependent signalling. Here, we determined the primary effects of HCM mutations on intracellular Ca2+ -handling and Ca2+ -dependent signalling in a model system possessing Ca2+ -handling mechanisms and contractile protein isoforms close to human in the absence of potentially confounding remodeling...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29753687/istaroxime-a-positive-inotropic-agent-devoid-of-proarrhythmic-properties-in-sensitive-chronic-atrioventricular-block-dogs
#4
Alexandre Bossu, Amée Kostense, Henriette D M Beekman, Marien J C Houtman, Marcel A G van der Heyden, Marc A Vos
Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na+ /K+ -transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP)...
May 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29752814/valproic-acid-inhibits-atp-triggered-ca-2-release-via-a-p38-dependent-mechanism-in-bend-3-endothelial-cells
#5
Iat-Lon Leong, Tien-Yao Tsai, Kar-Lok Wong, Lian-Ru Shiao, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling is hitherto unreported. In this report we examined the effects of VA on agonist-triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μM) did not cause an acute inhibition of ATP-triggered Ca2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size...
May 12, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29748131/underlying-mechanism-of-the-contractile-dysfunction-in-atrophied-ventricular-myocytes-from-a-murine-model-of-hypothyroidism
#6
Dolores Montalvo, Perla Pérez-Treviño, Katheryne Madrazo-Aguirre, Fabio A González-Mondellini, Hipólito O Miranda-Roblero, Diego Ramonfaur-Gracia, Mariana Jacobo-Antonio, Maritza Mayorga-Luna, Norma L Gómez-Víquez, Noemí García, Julio Altamirano
Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (Dmit ) and energy availability, is unclear...
February 5, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29748130/effects-of-the-iron-chelator-deferiprone-and-the-t-type-calcium-channel-blocker-efonidipine-on-cardiac-function-and-ca-2-regulation-in-iron-overloaded-thalassemic-mice
#7
Juthamas Khamseekaew, Sirinart Kumfu, Siripong Palee, Suwakon Wongjaikam, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
Although disturbance of cardiac Ca2+ regulation is involved in the pathophysiology of iron-overload cardiomyopathy, the obvious mechanisms involved in the dysregulation of iron-induced cardiac Ca2+ are unclear. Moreover, the roles of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac intracellular Ca2+ transients and Ca2+ regulatory proteins in thalassemic mice are still unknown. We tested the hypothesis that treatment with either deferiprone or efonidipine attenuated cardiac Ca2+ dysregulation and led to improved left ventricular (LV) function in iron-overloaded thalassemic mice...
February 6, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29727991/co-exposure-of-silica-nanoparticles-and-methylmercury-induced-cardiac-toxicity-in-vitro-and-in-vivo
#8
Xiaozhe Yang, Lin Feng, Yannan Zhang, Hejing Hu, Yanfeng Shi, Shuang Liang, Tong Zhao, Lige Cao, Junchao Duan, Zhiwei Sun
The released nanoparticles into environment can potentially interact with pre-existing pollution, maybe causing higher toxicity. As such, assessment of their joint toxic effects is necessary. This study was to investigate the co-exposure cardiac toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg). Factorial design was used to determine the potential joint action type. In vitro study, human cardiomyocytes (AC16) were exposed to SiNPs and MeHg alone or the combination. Higher toxicity was observed on cell viability, cell membrane damage in co-exposure compared with single exposure and control...
August 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29723871/cd38-cadpr-serca-signaling-axis-determines-skeletal-muscle-contractile-force-in-response-to-%C3%AE-adrenergic-stimulation
#9
Dae-Ryoung Park, Tae-Sik Nam, Ye-Won Kim, Seo-Ho Lee, Uh-Hyun Kim
BACKGROUND/AIMS: Cyclic ADP-ribose (cADPR) is a Ca2+ -mobilization messenger that acts on ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum (SR) Ca2+ stores. Moreover, it has been proposed that cADPR serves an additional role in activating the sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA) pump. The aim of this study was to determine the exact mechanism by which cADPR regulates SR Ca2+ stores in physiologically relevant systems. METHODS: We analyzed Ca2+ signals as well as the production of Ca2+ mobilizing messengers in the skeletal muscle cells of mice subjected to intensive exercise or in the SR fractions from skeletal muscle cells after β-adrenergic receptor (β-AR) stimulation...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29723491/qsox1-a-novel-actor-of-cardiac-protection-upon-acute-stress-in-mice
#10
Anais Caillard, Malha Sadoune, Arthur Cescau, Mehdi Meddour, Marine Gandon, Evelyne Polidano, Claude Delcayre, Kelly Da Silva, Philippe Manivet, Ana-Maria Gomez, Alain Cohen-Solal, Nicolas Vodovar, Zhenlin Li, Alexandre Mebazaa, Jane-Lise Samuel
QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion. The QSOX1-/- mice were viable but adult male exhibited a silent dilated cardiomyopathy. The QSOX1-/- hearts were characterized by low protein SERCA2a levels associated with a calcium homeostasis alteration, high levels of the endoplasmic reticulum (ER) chaperone proteins Grp78/Bip, and of the ER apoptosis sensor CHOP, indicating a chronic unfolded protein response (UPR)...
April 30, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29723269/17%C3%AE-estradiol-and-or-estrogen-receptor-alpha-signaling-blocks-protein-phosphatase-1-mediated-iso-induced-cardiac-hypertrophy
#11
Hsin-Yuan Fang, Meng-Yu Hung, Yueh-Min Lin, Sudhir Pandey, Chia-Chien Chang, Kuan-Ho Lin, Chia-Yao Shen, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29715473/stabilization-of-ca-2-signaling-in-cardiac-muscle-by-stimulation-of-serca
#12
Miguel Fernandez-Tenorio, Ernst Niggli
AIMS: In cardiac muscle, phosphorylation of the RyRs is proposed to increase their Ca2+ sensitivity. This mechanism could be arrhythmogenic via facilitation of spontaneous Ca2+ waves. Surprisingly, the level of Ca2+ inside the SR needed to initiate such waves has been reported to increase upon β-adrenergic stimulation, an observation which cannot be easily reconciled with elevated Ca2+ sensitivity of the RyRs. We tested the hypothesis that this change of Ca2+ wave threshold could occur indirectly, subsequent to SERCA stimulation...
April 30, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29699580/genetic-deletion-of-muscle-rank-or-selective-inhibition-of-rankl-is-not-as-effective-as-full-length-opg-fc-in-mitigating-muscular-dystrophy
#13
Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Anteneh Argaw, Dounia Hamoudi, Laetitia Marcadet, Daniel Gamu, Val A Fajardo, Hideo Yagita, Josef M Penninger, A Russell Tupling, Jérôme Frenette
Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that regulates synchronously bone and skeletal muscle physiopathology is still elusive. Receptor-activator of nuclear factor κB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG) are the key regulators of osteoclast differentiation and bone remodelling. We thus hypothesized that RANK/RANKL/OPG, which is a key pathway for bone regulation, is involved in Duchenne muscular dystrophy (DMD) physiopathology...
April 24, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29696147/drug-interactions-with-the-ca-2-atpase-from-sarco-endo-plasmic-reticulum-serca
#14
REVIEW
Francesco Tadini-Buoninsegni, Serena Smeazzetto, Roberta Gualdani, Maria Rosa Moncelli
The sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) is an intracellular membrane transporter that utilizes the free energy provided by ATP hydrolysis for active transport of Ca2+ ions from the cytoplasm to the lumen of sarco(endo)plasmic reticulum. SERCA plays a fundamental role for cell calcium homeostasis and signaling in muscle cells and also in cells of other tissues. Because of its prominent role in many physiological processes, SERCA dysfunction is associated to diseases displaying various degrees of severity...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29686704/the-change-of-left-ventricular-function-in-rats-with-subclinical-hypothyroid-and-the-effects-of-thyroxine-replacement
#15
Xuedi Chen, Cuixia Gao, Ningning Gong, Yu Wang, Limin Tian
Objective: The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Methods: Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29684447/type-3-iodothyronine-deiodinase-is-expressed-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#16
Kumiko Nishimura, Masafumi Takeda, Jun K Yamashita, Ichiro Shiojima, Nagaoki Toyoda
AIMS: Type 3 iodothyronine deiodinase (D3), which converts thyroxine (T4 ) and 3,5,3'-triiodothyronine (T3 ) to 3,3',5'-triiodothyronine (rT3 ) and 3,3'-diiodothyronine (T2 ), respectively, inactivates thyroid hormones. We investigated the expression and regulation of D3 in human cardiomyocytes which were differentiated from human induced pluripotent stem cells (hiPSCs). MAIN METHODS: We characterized D3 activity using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis...
April 20, 2018: Life Sciences
https://www.readbyqxmd.com/read/29675630/saikosaponin-d-inhibits-proliferation-by-up-regulating-autophagy-via-the-camkk%C3%AE-ampk-mtor-pathway-in-adpkd-cells
#17
Weiwei Shi, Dechao Xu, Junhui Gu, Cheng Xue, Bo Yang, Lili Fu, Shuwei Song, Dongmei Liu, Wei Zhou, Jiayi Lv, Ke Sun, Meihan Chen, Changlin Mei
Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy...
April 19, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29674140/impaired-ca-2-cycling-of-nonischemic-myocytes-contributes-to-sarcomere-dysfunction-early-after-myocardial-infarction
#18
Annette Kronenbitter, Florian Funk, Katarzyna Hackert, Simone Gorreßen, Dennis Glaser, Peter Boknik, Gereon Poschmann, Kai Stühler, Malgorzata Isić, Martina Krüger, Joachim P Schmitt
Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the role of myocyte Ca2+ handling in the remote myocardium 24 h after 60 min LAD occlusion. Cardiomyocytes isolated from the basal noninfarct-related parts of wild type mouse hearts demonstrated depressed beat-to-beat Ca2+ handling...
April 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29670896/short-term-treatment-with-esmolol-reverses-left-ventricular-hypertrophy-in-adult-spontaneously-hypertensive-rats-via-inhibition-of-akt-nf-%C3%AE%C2%BA-b-and-nfatc4
#19
Begoña Quintana-Villamandos, David A Goukassian, Sharath P Sasi, Emilio Delgado-Baeza
Our group has previously demonstrated that short-term treatment with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). The present study aimed to assess the molecular mechanisms related to this effect. Fourteen-month-old male SHRs were treated intravenously with saline as vehicle (SHR) or esmolol (SHR-E) (300  μ g/kg/min). Age-matched vehicle-treated male Wistar-Kyoto (WKY) rats served as controls. After 48 hours of treatment, the hearts were harvested and left ventricular tissue was separated and processed for Western blot analysis to determine the levels of Akt, NF- κ B, NFATc4, Creb1, Serca2a, Erk1/2, and Sapk/Jnk...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29663107/the-serca2-a-gatekeeper-of-neuronal-calcium-homeostasis-in-the-brain
#20
REVIEW
Aikaterini Britzolaki, Joseph Saurine, Emily Flaherty, Connor Thelen, Pothitos M Pitychoutis
Calcium (Ca2+ ) ions are prominent cell signaling regulators that carry information for a variety of cellular processes and are critical for neuronal survival and function. Furthermore, Ca2+ acts as a prominent second messenger that modulates divergent intracellular cascades in the nerve cells. Therefore, nerve cells have developed intricate Ca2+ signaling pathways to couple the Ca2+ signal to their biochemical machinery. Notably, intracellular Ca2+ homeostasis greatly relies on the rapid redistribution of Ca2+ ions into the diverse subcellular organelles which serve as Ca2+ stores, including the endoplasmic reticulum (ER)...
April 16, 2018: Cellular and Molecular Neurobiology
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