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https://www.readbyqxmd.com/read/27923914/widespread-control-of-calcium-signaling-by-a-family-of-serca-inhibiting-micropeptides
#1
Douglas M Anderson, Catherine A Makarewich, Kelly M Anderson, John M Shelton, Svetlana Bezprozvannaya, Rhonda Bassel-Duby, Eric N Olson
Micropeptides function as master regulators of calcium-dependent signaling in muscle. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), the membrane pump that promotes muscle relaxation by taking up Ca(2+) into the sarcoplasmic reticulum, is directly inhibited by three muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN), and sarcolipin (SLN). The widespread and essential function of SERCA across diverse cell types has raised questions as to how SERCA is regulated in cells that lack MLN, PLN, and SLN...
December 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27914790/sarcoplasmic-reticulum-ca-2-mg-2-k-and-cl-concentrations-adjust-quickly-as-heart-rate-changes
#2
Claudio Berti, Vilmos Zsolnay, Thomas R Shannon, Michael Fill, Dirk Gillespie
During systole, Ca(2+) is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) while, simultaneously, other ions (specifically K(+), Mg(2+), and Cl(-)) provide counter-ion flux. These ions move back into the SR during diastole through the SERCA pump and SR K(+) and Cl(-) channels. In homeostasis, all ion concentrations in different cellular regions (e.g., junctional and non-junctional SR, dyadic cleft, and cytosol) are the same at the beginning and end of the cardiac cycle. Here, we used an equivalent circuit compartment model of the SR and the surrounding cytoplasm to understand the heart rate dependence of SR ion homeostasis...
November 30, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27899691/high-throughput-spectral-and-lifetime-based-fret-screening-in-living-cells-to-identify-small-molecule-effectors-of-serca
#3
Tory M Schaaf, Kurt C Peterson, Benjamin D Grant, Prachi Bawaskar, Samantha Yuen, Ji Li, Joseph M Muretta, Gregory D Gillispie, David D Thomas
A robust high-throughput screening (HTS) strategy has been developed to discover small-molecule effectors targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA), based on a fluorescence microplate reader that records both the nanosecond decay waveform (lifetime mode) and the complete emission spectrum (spectral mode), with high precision and speed. This spectral unmixing plate reader (SUPR) was used to screen libraries of small molecules with a fluorescence resonance energy transfer (FRET) biosensor expressed in living cells...
November 29, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27872020/niclosamide-ethanolamine-inhibits-artery-constriction
#4
Shan-Liang Li, Jie Yan, Yan-Qiu Zhang, Chang-Lin Zhen, Ming-Yu Liu, Jing Jin, Jin-Lai Gao, Xiao-Lin Xiao, Xin Shen, Yu Tai, Nan Hu, Xin-Zi Zhang, Zhi-Jie Sun, De-Li Dong
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system...
November 18, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27862060/effect-of-bafilomycin-and-naadp-on-membrane-associated-atpases-and-respiration-of-isolated-mitochondria-of-the-murine-nemeth-kellner-lymphoma
#5
V Hreniukh, S Bychkova, O Kulachkovsky, A Babsky
: The goal of the study was to estimate the effect of a selective V-type H(+) -ATPase inhibitor bafilomycin A1 and nicotinic acid adenine dinucleotide phosphate (NAADP) on energetic processes in NK/Ly cell by directly measuring the respiration of isolated mitochondria and ATPase activities. NAADP (7 μM) increased the activity of Na(+) /K(+) -ATPase in the postmitochondrial fraction of NK/Ly cells, but lower concentration of NAADP decreased it (0.1 and 1 μM). The increase the activity of plasma membrane Ca(2)(+) ATPase (PMCA) under NAADP application (1 and 7 μM) was observed...
November 8, 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27861123/tecrl-a-new-life-threatening-inherited-arrhythmia-gene-associated-with-overlapping-clinical-features-of-both-lqts-and-cpvt
#6
Harsha D Devalla, Roselle Gélinas, Elhadi H Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie-A Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine J Monshouwer-Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jurg Schlaepfer, Christine L Mummery, Brian Stevenson, Zoltan Kutalik, Antoine Af de Vries, Léna Rivard, Arthur Am Wilde, Mario Talajic, Arie O Verkerk, Lihadh Al-Gazali, John D Rioux, Zahurul A Bhuiyan, Robert Passier
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27815070/direct-detection-of-serca-calcium-transport-and-small-molecule-inhibition-in-giant-unilamellar-vesicles
#7
Tengfei Bian, Joseph M Autry, Denise Casemore, Ji Li, David D Thomas, Gaohong He, Chengguo Xing
We have developed a charge-mediated fusion method to reconstitute the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in giant unilamellar vesicles (GUV). Intracellular Ca(2+) transport by SERCA controls key processes in human cells such as proliferation, signaling, and contraction. Small-molecule effectors of SERCA are urgently needed as therapeutics for Ca(2+) dysregulation in human diseases including cancer, diabetes, and heart failure. Here we report the development of a method for efficiently reconstituting SERCA in GUV, and we describe a streamlined protocol based on optimized parameters (e...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27802489/prolongation-of-relaxation-time-in-extraocular-muscles-with-brain-derived-neurotrophic-factor-in-adult-rabbit
#8
Krysta R Nelson, Shanlee M Stevens, Linda K McLoon
Purpose: We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM). Methods: One week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27776889/a-new-target-for-parkinson-s-disease-small-molecule-serca-activator-cdn1163-ameliorates-dyskinesia-in-6-ohda-lesioned-rats
#9
Russell Dahl
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(2+)-ATPase (SERCA) has been identified as a major cause of ER stress and neuron loss in PD...
October 12, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27747855/r%C3%A3-%C3%A5-nice-zale%C3%A5-ne-od-p%C3%A5-ci-w-uk%C3%A5-adzie-%C3%A5-ylnym-serca-potencjalne-wyt%C3%A5-umaczenie-dla-r%C3%A3-%C3%A5-nic-w-odpowiedzi-na-terapi%C3%A4-resynchronizuj%C3%A4-ca
#10
Agnieszka Młynarska, Rafał Młynarski, Krzysztof S Gołba, Maciej Sosnowski
BACKGROUND: We hypothesized that small differences in the anatomy of the coronary venous tree might be one of the factors responsible for the differences in the respond for cardiac resynchronization depending on a patient's gender. METHODS: The cardiac computed tomography scans with retrospective gating were performed on 315 subjects (aged 58.3 ± 11.6; 117 women) according to the clinical criteria. The standard protocol for coronary arteries was used during scanning...
October 17, 2016: Kardiologia Polska
https://www.readbyqxmd.com/read/27747307/neuronal-na-channels-are-integral-components-of-pro-arrhythmic-na-ca-2-signaling-nanodomain-that-promotes-cardiac-arrhythmias-during-%C3%AE-adrenergic-stimulation
#11
Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27731980/sarcolipin-promotes-uncoupling-of-the-serca-ca-2-pump-by-inducing-a-structural-rearrangement-in-the-energy-transduction-domain
#12
Joseph M Autry, David D Thomas, L Michel Espinoza-Fonseca
We have performed microsecond (μs) molecular dynamics simulation (MDS) to identify structural mechanisms for sarcolipin (SLN) uncoupling of Ca(2+) transport from ATP hydrolysis for the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). SLN regulates muscle metabolism and energy expenditure to provide resistance against diet-induced obesity and extreme cold. MDS demonstrated that the cytosolic domain of SLN induces a salt bridge-mediated structural rearrangement in the energy-transduction domain of SERCA. We propose that this structural change uncouples SERCA by perturbing Ca(2+) occlusion at residue E309 in transport site II, thus facilitating Ca(2+) backflux to the cytosol...
October 28, 2016: Biochemistry
https://www.readbyqxmd.com/read/27729868/the-autonomic-nervous-system-regulates-the-heart-rate-through-camp-pka-dependent-and-independent-coupled-clock-pacemaker-cell-mechanisms
#13
Joachim Behar, Ambhighainath Ganesan, Jin Zhang, Yael Yaniv
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation)...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27694578/redox-assisted-regulation-of-ca2-homeostasis-in-the-endoplasmic-reticulum-by-disulfide-reductase-erdj5
#14
Ryo Ushioda, Akitoshi Miyamoto, Michio Inoue, Satoshi Watanabe, Masaki Okumura, Ken-Ichi Maegawa, Kaiku Uegaki, Shohei Fujii, Yasuko Fukuda, Masataka Umitsu, Junichi Takagi, Kenji Inaba, Katsuhiko Mikoshiba, Kazuhiro Nagata
Calcium ion (Ca(2+)) is an important second messenger that regulates numerous cellular functions. Intracellular Ca(2+) concentration ([Ca(2+)]i) is strictly controlled by Ca(2+) channels and pumps on the endoplasmic reticulum (ER) and plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase (SERCA), imports Ca(2+) from the cytosol into the ER in an ATPase activity-dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is negatively regulated by disulfide bond formation between two luminal cysteines...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27694214/dyssynchronous-calcium-removal-in-heart-failure-induced-atrial-remodeling
#15
F Hohendanner, J DeSantiago, F R Heinzel, L A Blatter
We tested the hypothesis that in atrial myocytes from a rabbit left ventricular heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca removal during excitation-contraction coupling together with increased Na/Ca exchange (NCX) activity generate a substrate for proarrhythmic Ca release. Ca removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via NCX exclusively in the cell periphery since rabbit atrial myocytes lack transverse tubules. Ca removal kinetics were assessed by the time constant τ of decay of local peripheral subsarcolemmal (SS) and central (CT) action potential (AP)-induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo-4)...
December 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27688314/genotype-dependent-and-independent-calcium-signaling-dysregulation-in-human-hypertrophic-cardiomyopathy
#16
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27686750/caffeoylquinic-acids-from-antiplasmodial-active-extract-of-xanthium-cavanillesii-fruits-and-their-molecular-modelling-studies
#17
Alex Gutterres Taranto, Sônia Carine Cova Costa, Franco Henrique Andrade Leite, Matheus Santos de Sá, Milena Botelho Pereira Soares, Miriam Moreira Mussi, Alexsandro Branco
The antiplasmodial active extract of Xanthium cavanillesii contains 3,4-dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and 1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to investigate the interaction of these molecules with a promising validated target of Plasmodium, PfATP6 orthologue of mammalian Ca(+2)-ATPase. Models of this receptor were obtained through comparative modelling. Afterwards, molecular docking studies were used to identify possible interaction modes of these caffeoyl quinic derivatives on the binding site...
August 13, 2016: Natural Product Research
https://www.readbyqxmd.com/read/27677409/angptl2-activity-in-cardiac-pathologies-accelerates-heart-failure-by-perturbing-cardiac-function-and-energy-metabolism
#18
Zhe Tian, Keishi Miyata, Tsuyoshi Kadomatsu, Haruki Horiguchi, Hiroyuki Fukushima, Shugo Tohyama, Yoshihiro Ujihara, Takahiro Okumura, Satoshi Yamaguchi, Jiabin Zhao, Motoyoshi Endo, Jun Morinaga, Michio Sato, Taichi Sugizaki, Shunshun Zhu, Kazutoyo Terada, Hisashi Sakaguchi, Yoshihiro Komohara, Motohiro Takeya, Naoki Takeda, Kimi Araki, Ichiro Manabe, Keiichi Fukuda, Kinya Otsu, Jun Wada, Toyoaki Murohara, Satoshi Mohri, Jun K Yamashita, Motoaki Sano, Yuichi Oike
A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice...
September 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27653478/cardiac-calcium-atpase-dimerization-measured-by-cross-linking-and-fluorescence-energy-transfer
#19
Daniel J Blackwell, Taylor J Zak, Seth L Robia
The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers...
September 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27644036/demethoxycurcumin-is-a-potent-inhibitor-of-p-type-atpases-from-diverse-kingdoms-of-life
#20
Trong Tuan Dao, Pankaj Sehgal, Truong Thanh Tung, Jesper Vuust Møller, John Nielsen, Michael Palmgren, Søren Brøgger Christensen, Anja Thoe Fuglsang
P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs. In this work a library of natural compounds was screened and we first identified curcuminoids as plasma membrane H+-ATPases inhibitors in plant and fungal cells. We also found that some of the commercial curcumins contain several curcuminoids...
2016: PloS One
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