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https://www.readbyqxmd.com/read/27882934/macrophage-dependent-il-1%C3%AE-production-induces-cardiac-arrhythmias-in-diabetic-mice
#1
Gustavo Monnerat, Micaela L Alarcón, Luiz R Vasconcellos, Camila Hochman-Mendez, Guilherme Brasil, Rosana A Bassani, Oscar Casis, Daniela Malan, Leonardo H Travassos, Marisa Sepúlveda, Juan Ignacio Burgos, Martin Vila-Petroff, Fabiano F Dutra, Marcelo T Bozza, Claudia N Paiva, Adriana Bastos Carvalho, Adriana Bonomo, Bernd K Fleischmann, Antonio Carlos Campos de Carvalho, Emiliano Medei
Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27815365/xanthohumol-modulates-calcium-signaling-in-rat-ventricular-myocytes-possible-antiarrhythmic-properties
#2
Juan Jose Arnaiz-Cot, Lars Cleemann, Martin Morad
Cardiac arrhythmia is a major cause of mortality in cardiovascular pathologies. A host of drugs targeted to sarcolemmal Na(+), Ca(2+), and K(+) channels have had limited success clinically. Recently, Ca(2+) signaling has been target of pharmacotherapy based on finding that leaky ryanodine receptors elevate local Ca(2+) concentrations causing membrane depolarizations that trigger arrhythmias. Here we report that xanthohumol, an antioxidant extracted from hops and showing therapeutic effects in other pathologies, may have antiarrhythmic properties by stabilizing ryanodine receptor's activity...
November 4, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27802169/junctophilin-2-in-the-nanoscale-organisation-and-functional-signalling-of-ryanodine-receptor-clusters-in-cardiomyocytes
#3
Michelle L Munro, Isuru D Jayasinghe, Qiongling Wang, Ann Quick, Wei Wang, David Baddeley, Xander H T Wehrens, Christian Soeller
Signalling nanodomains requiring close contact between the plasma membrane and internal compartments, known as 'junctions', are fast communication hubs within excitable cells such as neurones and muscle. Here, we have examined two transgenic murine models probing the role of junctophilin-2, a membrane-tethering protein crucial for the formation and molecular organisation of sub-microscopic junctions in ventricular muscle cells of the heart. Quantitative single-molecule localisation microscopy showed that junctions in animals producing above-normal levels of junctophilin-2 were enlarged, allowing the re-organisation of the primary functional protein within it, the ryanodine receptor (RyR; in this paper, we use RyR to refer to the myocardial isoform RyR2)...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27762397/a-unified-theory-of-calcium-alternans-in-ventricular-myocytes
#4
Zhilin Qu, Michael B Liu, Michael Nivala
Intracellular calcium (Ca(2+)) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca(2+) cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca(2+) alternans. Two mechanisms of Ca(2+) alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca(2+) release and uptake, and the other on refractoriness and other properties of Ca(2+) sparks...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27738055/a-novel-calcium-dependent-kinase-inhibitor-1517-cures-cryptosporidiosis-in-immunosuppressed-mice
#5
A Castellanos-Gonzalez, H Sparks, S Nava, W Huang, Z Zhang, K Rivas, M Hulverson, L Barrett, K K Ojo, E Fan, W C Van Voorhis, A C White
Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side-chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKI) that selectively target CDPK1...
October 12, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27729468/striated-muscle-preferentially-expressed-protein-kinase-speg-is-essential-for-cardiac-function-by-regulating-junctional-membrane-complex-activity
#6
Ann P Quick, Qiongling Wang, Leonne E Philippen, Giselle Barreto-Torres, David Y Chiang, David L Beavers, Guoliang Wang, Maha Khalid, Julia O Reynolds, Hannah M Campbell, Jordan Showell, Mark D McCauley, Arjen Scholten, Xander H Wehrens
RATIONALE: Junctional membrane complexes (JMC) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein striated muscle preferentially expressed gene (SPEG) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. MMethods and Results: Proteomic analysis of immunoprecipatated JMC-proteins ryanodine receptor type-2 (RyR2) and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins...
October 11, 2016: Circulation Research
https://www.readbyqxmd.com/read/27711080/adeno-associated-virus-mediated-casq2-delivery-rescues-phenotypic-alterations-in-a-patient-specific-model-of-recessive-catecholaminergic-polymorphic-ventricular-tachycardia
#7
Francesco Lodola, Diego Morone, Marco Denegri, Rossana Bongianino, Hiroko Nakahama, Lucia Rutigliano, Rosanna Gosetti, Giulia Rizzo, Alessandra Vollero, Michelangelo Buonocore, Carlo Napolitano, Gianluigi Condorelli, Silvia G Priori, Elisa Di Pasquale
Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation...
October 6, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27612843/titanium-dental-implant-surfaces-obtained-by-anodic-spark-deposition-from-the-past-to-the-future
#8
REVIEW
Milena R Kaluđerović, Joachim P Schreckenbach, Hans-Ludwig Graf
Commercial titanium-based dental implants are obtained applying various methods such as machining, acid etching, anodization, plasma spraying, grit blasting or combination techniques yielding materials with smooth or micro-roughened surfaces. Those techniques are used to optimize the surface properties and to maximize biocompatibility and bioactivity with bone tissue. Present review is focused on the material surfaces obtained by anodic spark deposition (ASD). From the early 1980s till present, the results of numerous studies have shown that anodically oxidized surfaces with different dopants express a positive effect on osteoblasts behavior in vitro and osseointegration in vivo...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/27377851/modeling-na-ca-2-exchange-in-the-heart-allosteric-activation-spatial-localization-sparks-and-excitation-contraction-coupling
#9
Lulu Chu, Joseph L Greenstein, Raimond L Winslow
The cardiac sodium (Na(+))/calcium (Ca(2+)) exchanger (NCX1) is an electrogenic membrane transporter that regulates Ca(2+) homeostasis in cardiomyocytes, serving mainly to extrude Ca(2+) during diastole. The direction of Ca(2+) transport reverses at membrane potentials near that of the action potential plateau, generating an influx of Ca(2+) into the cell. Therefore, there has been great interest in the possible roles of NCX1 in cardiac Ca(2+)-induced Ca(2+) release (CICR). Interest has been reinvigorated by a recent super-resolution optical imaging study suggesting that ~18% of NCX1 co-localize with ryanodine receptor (RyR2) clusters, and ~30% of additional NCX1 are localized to within ~120nm of the nearest RyR2...
July 1, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27368417/a-novel-mouse-model-of-the-aged-brain-over-expression-of-the-l-type-voltage-gated-calcium-channel-cav1-3
#10
Jamie N Krueger, Shannon J Moore, Rachel Parent, Brandon C McKinney, Amy Lee, Geoffrey G Murphy
The aged population is growing rapidly, which has sparked tremendous interest in elucidating mechanisms of aging in both the body and the brain. Animal models have become an indispensable tool in biomedical science, but because of the cost and extended timeframe associated with aging animals to appropriate time points, studies that rely on using aged animals are often not feasible. Somewhat surprisingly, there are relatively few animal models that have been specifically engineered to mimic physiological changes known to occur during "normal" aging...
June 28, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27347901/role-of-mitochondria-in-cerebral-vascular-function-energy-production-cellular-protection-and-regulation-of-vascular-tone
#11
David W Busija, Ibolya Rutkai, Somhrita Dutta, Prasad V Katakam
Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms...
2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27322594/electrophysiological-basis-of-metabolic-syndrome-induced-cardiac-dysfunction
#12
Esma N Okatan, Aysegul Toy Durak, Belma Turan
Myocardial contractility is controlled by intracellular Ca(2+) cycling with the contribution of sarcoplasmic reticulum (SR). In this study, we aimed to investigate the role of altered SR function in defective regulation of intracellular Ca(2+) levels in rats with metabolic syndrome (MetS) induced by a 16-week high-sucrose drinking-water diet. Electric-field stimulated transient intracellular Ca(2+) changes in MetS cardiomyocytes exhibited significantly reduced amplitude (∼30%) and prolonged time courses (2-fold), as well as depressed SR Ca(2+) loading (∼55%) with increased basal Ca(2+) level...
April 12, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27242324/role-of-serca-and-the-sarcoplasmic-reticulum-calcium-content-on-calcium-waves-propagation-in-rat-ventricular-myocytes
#13
Ayleen Salazar-Cantú, Perla Pérez-Treviño, Dolores Montalvo-Parra, Jaime Balderas-Villalobos, Norma L Gómez-Víquez, Noemí García, Julio Altamirano
In Ca(2+)-overloaded ventricular myocytes, SERCA is crucial to steadily achieve the critical sarcoplasmic reticulum (SR) Ca(2+) level to trigger and sustain Ca(2+) waves, that propagate at constant rate (ʋwave). High luminal Ca(2+) sensitizes RyR2, thereby increasing Ca(2+) sparks frequency, and the larger RyR2-mediated SR Ca(2+) flux (dF/dt) sequentially activates adjacent RyR2 clusters. Recently, it was proposed that rapid SERCA Ca(2+) reuptake, ahead of the wave front, further sensitizes RyR2, increasing ʋwave...
August 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27237957/effect-of-flecainide-derivatives-on-sarcoplasmic-reticulum-calcium-release-suggests-a-lack-of-direct-action-on-the-cardiac-ryanodine-receptor
#14
Mark L Bannister, Anita Alvarez-Laviada, N Lowri Thomas, Sammy A Mason, Sharon Coleman, Christo L du Plessis, Abbygail T Moran, David Neill-Hall, Hasnah Osman, Mark C Bagley, Kenneth T MacLeod, Christopher H George, Alan J Williams
BACKGROUND AND PURPOSE: Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels...
August 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27154230/mitochondrial-oxidative-stress-during-cardiac-lipid-overload-causes-intracellular-calcium-leak-and-arrhythmia
#15
Leroy C Joseph, Prakash Subramanyam, Christopher Radlicz, Chad M Trent, Vivek Iyer, Henry M Colecraft, John P Morrow
BACKGROUND: Diabetes and obesity are associated with an increased risk of arrhythmia and sudden cardiac death. Abnormal lipid accumulation is observed in cardiomyocytes of obese and diabetic patients, which may contribute to arrhythmia, but the mechanisms are poorly understood. A transgenic mouse model of cardiac lipid overload, the peroxisome proliferator-activated receptor-γ (PPARg) cardiac overexpression mouse, has long QT and increased ventricular ectopy. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that the increase in ventricular ectopy during cardiac lipid overload is caused by abnormalities in calcium handling due to increased mitochondrial oxidative stress...
August 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27121757/calcium-calmodulin-dependent-kinase-ii-and-nitric-oxide-synthase-1-dependent-modulation-of-ryanodine-receptors-during-%C3%AE-adrenergic-stimulation-is-restricted-to-the-dyadic-cleft
#16
Eef Dries, Demetrio J Santiago, Daniel M Johnson, Guillaume Gilbert, Patricia Holemans, Sanne M Korte, H Llewelyn Roderick, Karin R Sipido
In cardiac myocytes, β-adrenergic stimulation enhances Ca(2+) cycling through an integrated signalling cascade modulating L-type Ca(2+) channels (LTCC), phospholamban, and ryanodine receptors (RyRs). CaMKII and nitric oxide synthase1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca(2+) microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca(2+) ]i indicator...
April 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27113677/the-zinc-spark-is-an-inorganic-signature-of-human-egg-activation
#17
Francesca E Duncan, Emily L Que, Nan Zhang, Eve C Feinberg, Thomas V O'Halloran, Teresa K Woodruff
Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent "zinc spark...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26987302/the-fertilization-induced-zinc-spark-is-a-novel-biomarker-of-mouse-embryo-quality-and-early-development
#18
Nan Zhang, Francesca E Duncan, Emily L Que, Thomas V O'Halloran, Teresa K Woodruff
Upon activation, mammalian eggs release billions of zinc ions in an exocytotic event termed the "zinc spark." The zinc spark is dependent on and occurs coordinately with intracellular calcium transients, which are tightly associated with embryonic development. Thus, we hypothesized that the zinc spark represents an early extracellular physicochemical marker of the developmental potential of the zygote. To test this hypothesis, we monitored zinc exocytosis in individual mouse eggs following parthenogenetic activation or in vitro fertilization (IVF) and tracked their development...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26829967/effect-upon-biocompatibility-and-biocorrosion-properties-of-plasma-electrolytic-oxidation-in-trisodium-phosphate-electrolytes
#19
Yu-Kyoung Kim, Il-Song Park, Kwang-Bok Lee, Tae-Sung Bae, Yong-Seok Jang, Young-Min Oh, Min-Ho Lee
Surface modification to improve the corrosion resistance and biocompatibility of the Mg-Al-Zn-Ca alloy was conducted via plasma electrolytic oxidation (PEO) in an electrolyte that included phosphate. Calcium phosphate can be easily induced on the surface of a PEO coating that includes phosphate in a physiological environment because Ca(2+) ions in body fluids can be combined with PO4 (3-). Cytotoxicity of the PEO coating formed in electrolytes with various amounts of Na3PO4 was identified. In particular, the effects that PEO films have upon oxidative stress and differentiation of osteoblast activity were studied...
March 2016: Biointerphases
https://www.readbyqxmd.com/read/26827896/ryanodine-receptor-sensitivity-governs-the-stability-and-synchrony-of-local-calcium-release-during-cardiac-excitation-contraction-coupling
#20
Andrew P Wescott, M Saleet Jafri, W J Lederer, George S B Williams
Calcium-induced calcium release is the principal mechanism that triggers the cell-wide [Ca(2+)]i transient that activates muscle contraction during cardiac excitation-contraction coupling (ECC). Here, we characterize this process in mouse cardiac myocytes with a novel mathematical action potential (AP) model that incorporates realistic stochastic gating of voltage-dependent L-type calcium (Ca(2+)) channels (LCCs) and sarcoplasmic reticulum (SR) Ca(2+) release channels (the ryanodine receptors, RyR2s). Depolarization of the sarcolemma during an AP stochastically activates the LCCs elevating subspace [Ca(2+)] within each of the cell's 20,000 independent calcium release units (CRUs) to trigger local RyR2 opening and initiate Ca(2+) sparks, the fundamental unit of triggered Ca(2+) release...
March 2016: Journal of Molecular and Cellular Cardiology
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