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https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#1
David R de Alba-Aguayo, Natalia Pavón, Martha Mercado-Morales, Miyamin Miranda-Saturnino, Mavil López-Casamichana, Agustin Guerrero-Hernández, Angelica Rueda
INTRODUCTION: Calcium (Ca(2+)) leak during cardiac diastole is chiefly mediated by intracellular Ca(2+) channel/Ryanodine Receptors. Increased diastolic Ca(2+) leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca(2+) leak and the specific roles played by key intracellular Ca(2+)-handling proteins in hyperthyroidism, a known arrhythmogenic condition. AIM: We sought to determine whether there were modifications in diastolic Ca(2+) leak, based on the recording of Ca(2+) sparks and Ca(2+) waves; we also investigated changes in the expression and activity of key Ca(2+) handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca(2+) ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28159581/recombinant-expression-of-intrepicalcin-from-the-scorpion-vaejovis-intrepidus-and-its-effect-on-skeletal-ryanodine-receptors
#2
Leonel Vargas-Jaimes, Liang Xiao, Jing Zhang, Lourival D Possani, Héctor H Valdivia, Verónica Quintero-Hernández
BACKGROUND: Scorpion venoms contain toxins that modulate ionic channels, among which are the calcins, a small group of short, basic peptides with an Inhibitor Cystine Knot (ICK) motif that target calcium release channels/ryanodine receptors (RyRs) with high affinity and selectivity. Here we describe the heterologous expression of Intrepicalcin, identified by transcriptomic analysis of venomous glands from Vaejovis intrepidus. METHODS: Recombinant Intrepicalcin was obtained in Escherichia coli BL21-DE3 (periplasm) by fusing the Intrepicalcin gene to sequences coding for signal-peptide, thioredoxin, His-tag and enterokinase cleavage site...
January 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28143888/divergent-mechanisms-leading-to-signaling-dysfunction-in-embryonic-muscle-by-bisphenol-a-and-tetrabromobisphenol-a
#3
Rui Zhang, Isaac N Pessah
Bisphenol A (BPA) and its brominated derivative tetrabromobisphenol A (TBBPA) are high production volume chemicals utilized in the manufacture of various consumer products. Although regarded as endocrine disruptors, these chemicals are suspected to exert non-genomic actions on muscle function that are not well understood. Using skeletal muscle microsomes, we examined the effects of BPA and TBBPA on ryanodine receptor type 1 (RyR1), dihydropyridine receptor (DHPR), and sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA)...
January 31, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28131630/the-effect-of-pka-mediated-phosphorylation-of-ryanodine-receptor-on-sr-ca-2-leak-in-ventricular-myocytes
#4
Elisa Bovo, Sabine Huke, Lothar A Blatter, Aleksey V Zima
Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca(2+) release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca(2+)] and intra-SR [Ca(2+)]SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies...
January 25, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28126160/role-of-nod1-in-heart-failure-progression-via-regulation-of-ca-2-handling
#5
Almudena Val-Blasco, María Jose G M Piedras, Gema Ruiz-Hurtado, Natalia Suarez, Patricia Prieto, Silvia Gonzalez-Ramos, Nieves Gómez-Hurtado, Carmen Delgado, Laetitia Pereira, Gemma Benito, Carlos Zaragoza, Nieves Domenech, María Generosa Crespo-Leiro, Daniel Vasquez-Echeverri, Gabriel Nuñez, Eduardo Lopez-Collazo, Lisardo Boscá, María Fernández-Velasco
BACKGROUND: Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases. OBJECTIVES: This study evaluated the role of NOD1 in HF progression. METHODS: NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1(-/-) mice (Nod1(-/-)-PMI)...
January 31, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28105734/calcium-calmodulin-dependent-protein-kinase-mediates-the-intracellular-signaling-pathways-of-cardiac-apoptosis-in-mice-with-impaired-glucose-tolerance
#6
Marilen Federico, Enrique L Portiansky, Leandro Sommese, Francisco J Alvarado, Paula G Blanco, Carolina N Zanuzzi, John Dedman, Marcia Kaetzel, Xander H T Wehrens, Alicia Mattiazzi, Julieta Palomeque
Background The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We described that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca(2+) /calmodulin-protein kinase (CaMKII) activity, ryanodine receptors (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca(2+) leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. Methods and Results We generated a pre-diabetic model in mice fed with FRD...
January 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28102477/potential-new-mechanisms-of-pro-arrhythmia-in-arrhythmogenic-cardiomyopathy-focus-on-calcium-sensitive-pathways
#7
REVIEW
C J M van Opbergen, M Delmar, T A B van Veen
Arrhythmogenic cardiomyopathy, or its most well-known subform arrhythmogenic right ventricular cardiomyopathy (ARVC), is a cardiac disease mainly characterised by a gradual replacement of the myocardial mass by fibrous and fatty tissue, leading to dilatation of the ventricular wall, arrhythmias and progression towards heart failure. ARVC is commonly regarded as a disease of the intercalated disk in which mutations in desmosomal proteins are an important causative factor. Interestingly, the Dutch founder mutation PLN R14Del has been identified to play an additional, and major, role in ARVC patients within the Netherlands...
January 19, 2017: Netherlands Heart Journal
https://www.readbyqxmd.com/read/27881388/hyperglycemia-induces-defective-ca2-homeostasis-in-cardiomyocytes
#8
Andrea Sorrentino, Giulia Borghetti, Yu Zhou, Antonio Cannata, Marianna Meo, Sergio Signore, Piero Anversa, Annarosa Leri, Polina Goichberg, Khaled Qanud, Jason T Jacobson, Thomas H Hintze, Marcello Rota
: Diabetes and other metabolic conditions characterized by elevated blood glucose constitute important risk factors for cardiovascular disease. Hyperglycemia targets myocardial cells rendering ineffective mechanical properties of the heart, but cellular alterations dictating the progressive deterioration of cardiac function with metabolic disorders remain to be clarified. In the current study, we examined the effects of hyperglycemia on cardiac function and myocyte physiology by employing mice with high blood glucose induced by administration of streptozotocin, a compound toxic to insulin-producing β-cells...
January 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27816525/enhanced-nucleoplasmic-ca-2-signaling-in-ventricular-myocytes-from-young-hypertensive-rats
#9
Jelena Plačkić, Sebastian Preissl, Yulia Nikonova, Florentina Pluteanu, Lutz Hein, Jens Kockskämper
Arterial hypertension causes left ventricular (LV) myocyte hypertrophy. Alterations in nuclear Ca(2+) may be involved in regulation of histone acetylation, transcription and hypertrophy. Regulation of nuclear Ca(2+) in hypertension, however, is unknown. Therefore, we elucidated cellular mechanisms underlying nuclear Ca(2+) regulation in LV myocytes from hypertensive versus normotensive rats and evaluated possible consequences for Ca(2+)-dependent regulation of histone acetylation. LV myocytes and myocyte nuclei were isolated from young spontaneously hypertensive rats (SHR) shortly after development of hypertension...
December 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27799555/cardiac-electrical-defects-in-progeroid-mice-and-hutchinson-gilford-progeria-syndrome-patients-with-nuclear-lamina-alterations
#10
José Rivera-Torres, Conrado J Calvo, Anna Llach, Gabriela Guzmán-Martínez, Ricardo Caballero, Cristina González-Gómez, Luis J Jiménez-Borreguero, Juan A Guadix, Fernando G Osorio, Carlos López-Otín, Adela Herraiz-Martínez, Nuria Cabello, Alex Vallmitjana, Raul Benítez, Leslie B Gordon, José Jalife, José M Pérez-Pomares, Juan Tamargo, Eva Delpón, Leif Hove-Madsen, David Filgueiras-Rama, Vicente Andrés
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24(-/-) mouse model of HGPS. Challenge of Zmpste24(-/-) mice with the β-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27491078/a-human-pluripotent-stem-cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-recapitulates-patient-specific-drug-responses
#11
Marcela K Preininger, Rajneesh Jha, Joshua T Maxwell, Qingling Wu, Monalisa Singh, Bo Wang, Aarti Dalal, Zachary T Mceachin, Wilfried Rossoll, Chadwick M Hales, Peter S Fischbach, Mary B Wagner, Chunhui Xu
Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs...
September 1, 2016: Disease Models & Mechanisms
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/27235390/k201-jtv519-is-a-ca2-dependent-blocker-of-serca-and-a-partial-agonist-of-ryanodine-receptors-in-striated-muscle
#13
Yuanzhao L Darcy, Paula L Diaz-Sylvester, Julio A Copello
K201 (JTV-519) may prevent abnormal Ca(2+) leak from the sarcoplasmic reticulum (SR) in the ischemic heart and skeletal muscle (SkM) by stabilizing the ryanodine receptors (RyRs; RyR1 and RyR2, respectively). We tested direct modulation of the SR Ca(2+)-stimulated ATPase (SERCA) and RyRs by K201. In isolated cardiac and SkM SR microsomes, K201 slowed the rate of SR Ca(2+) loading, suggesting potential SERCA block and/or RyR agonism. K201 displayed Ca(2+)-dependent inhibition of SERCA-dependent ATPase activity, which was measured in microsomes incubated with 200, 2, and 0...
August 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27171264/ischemic-postconditioning-protects-the-heart-against-ischemia-reperfusion-injury-via-neuronal-nitric-oxide-synthase-in-the-sarcoplasmic-reticulum-and-mitochondria
#14
L Hu, J Wang, H Zhu, X Wu, L Zhou, Y Song, S Zhu, M Hao, C Liu, Y Fan, Y Wang, Q Li
As a result of its spatial confinement in cardiomyocytes, neuronal nitric oxide synthase (nNOS) is thought to regulate mitochondrial and sarcoplasmic reticulum (SR) function by maintaining nitroso-redox balance and Ca(2+) cycling. Thus, we hypothesize that ischemic postconditioning (IPostC) protects hearts against ischemic/reperfusion (I/R) injury through an nNOS-mediated pathway. Isolated mouse hearts were subjected to I/R injury in a Langendorff apparatus, H9C2 cells and primary neonatal rat cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27169737/constitutive-intracellular-na-excess-in-purkinje-cells-promotes-arrhythmogenesis-at-lower-levels-of-stress-than-ventricular-myocytes-from-mice-with-catecholaminergic-polymorphic-ventricular-tachycardia
#15
B Cicero Willis, Sandeep V Pandit, Daniela Ponce-Balbuena, Manuel Zarzoso, Guadalupe Guerrero-Serna, Bijay Limbu, Makarand Deo, Emmanuel Camors, Rafael J Ramirez, Sergey Mironov, Todd J Herron, Héctor H Valdivia, José Jalife
BACKGROUND: In catecholaminergic polymorphic ventricular tachycardia (CPVT), cardiac Purkinje cells (PCs) appear more susceptible to Ca(2+) dysfunction than ventricular myocytes (VMs). The underlying mechanisms remain unknown. Using a CPVT mouse (RyR2(R4496C+/Cx40eGFP)), we tested whether PC intracellular Ca(2+) ([Ca(2+)]i) dysregulation results from a constitutive [Na(+)]i surplus relative to VMs. METHODS AND RESULTS: Simultaneous optical mapping of voltage and [Ca(2+)]i in CPVT hearts showed that spontaneous Ca(2+) release preceded pacing-induced triggered activity at subendocardial PCs...
June 14, 2016: Circulation
https://www.readbyqxmd.com/read/27166817/effects-of-modified-parvalbumin-ef-hand-motifs-on-cardiac-myocyte-contractile-function
#16
Michelle L Asp, Frances V Sjaastad, Jalal K Siddiqui, Jonathan P Davis, Joseph M Metzger
Cardiac gene delivery of parvalbumin (Parv), an EF-hand Ca(2+) buffer, has been studied as a therapeutic strategy for diastolic heart failure, in which slow Ca(2+) reuptake is an important contributor. A limitation of wild-type (WT) Parv is the significant trade-off between faster relaxation and blunted contraction amplitude, occurring because WT-Parv sequesters Ca(2+) too early in the cardiac cycle and prematurely truncates sarcomere shortening in the facilitation of rapid relaxation. We recently demonstrated that an E → Q substitution (ParvE101Q) at amino acid 12 of the EF-hand Ca(2+)/Mg(2+) binding loop disrupts bidentate Ca(2+) binding, reducing Ca(2+) affinity by 99-fold and increasing Mg(2+) affinity twofold...
May 10, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27114612/structure-function-relationships-of-peptides-forming-the-calcin-family-of-ryanodine-receptor-ligands
#17
Liang Xiao, Georgina B Gurrola, Jing Zhang, Carmen R Valdivia, Mario SanMartin, Fernando Z Zamudio, Liming Zhang, Lourival D Possani, Héctor H Valdivia
Calcins are a novel family of scorpion peptides that bind with high affinity to ryanodine receptors (RyRs) and increase their activity by inducing subconductance states. Here, we provide a comprehensive analysis of the structure-function relationships of the eight calcins known to date, based on their primary sequence, three-dimensional modeling, and functional effects on skeletal RyRs (RyR1). Primary sequence alignment and evolutionary analysis show high similarity among all calcins (≥78.8% identity). Other common characteristics include an inhibitor cysteine knot (ICK) motif stabilized by three pairs of disulfide bridges and a dipole moment (DM) formed by positively charged residues clustering on one side of the molecule and neutral and negatively charged residues segregating on the opposite side...
May 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27108787/na-permeates-through-l-type-ca-2-channel-in-bovine-airway-smooth-muscle
#18
Bettina Sommer, Edgar Flores-Soto, Jorge Reyes-García, Verónica Díaz-Hernández, Verónica Carbajal, Luis M Montaño
UNLABELLED: Membrane depolarization of airway smooth muscle (ASM) opens L-type voltage dependent Ca(2+) channels (L-VDCC) allowing Ca(2+) entrance to produce contraction. In Ca(2+) free conditions Na(+) permeates through L-VDCC in excitable and non-excitable cells and this phenomenon is annulled at µM Ca(2+) concentrations. Membrane depolarization also induces activation of Gq proteins and sarcoplasmic reticulum Ca(2+) release. In bovine ASM, KCl induced a transient contraction sensitive to nifedipine in Ca(2+)free medium, indicating an additional mechanism to the SR-Ca(2+) release...
July 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27099074/impaired-ca-2-homeostasis-and-decreased-orai1-expression-modulates-arterial-hyporeactivity-to-vasoconstrictors-during-endotoxemia
#19
Arthur Oliveira Nonato, Vania C Olivon, Vanessa Dela Justina, Camila Z Zanotto, R Clinton Webb, Rita C Tostes, Victor V Lima, Fernanda R Giachini
We hypothesized that SIRS/endotoxemia-associated hyporesponsiveness to vasoconstrictors is mediated by smaller increases in intracellular Ca(2+) levels due to reduced signaling via the STIM/Orai. Male Wistar rats were injected either with saline or bacterial LPS (i.p.; 10 mg/kg), and experiments were performed 24 h later. LPS-injected rats exhibited decreased systolic blood pressure, increased heart rate, neutrophils' migration into the peritoneal cavity, and elevated alanine aminotransferase levels. Additionally, second-order mesenteric arteries from endotoxemic rats displayed hyporeactivity to contractile agents such as phenylephrine and potassium chloride; decreased contractile responses to Ca(2+); reduced contraction during Ca(2+) loading; and smaller intracellular Ca(2+) stores...
June 2016: Inflammation
https://www.readbyqxmd.com/read/26968444/1-2-dichlorobenzene-affects-the-formation-of-the-phosphoenzyme-stage-during-the-catalytic-cycle-of-the-ca-2-atpase-from-sarcoplasmic-reticulum
#20
Javier Vargas-Medrano, Jorge A Sierra-Fonseca, Luis F Plenge-Tellechea
BACKGROUND: 1,2-Dichlorobenzene (1,2-DCB) is a benzene-derived molecule with two Cl atoms that is commonly utilized in the synthesis of pesticides. 1,2-DCB can be absorbed by living creatures and its effects on naturally-occurring enzymatic systems, including the effects on Ca(2+)-ATPases, have been poorly studied. Therefore, we aimed to study the effect of 1,2-DCB on the Ca(2+)-ATPase from sarcoplasmic reticulum (SERCA), a critical regulator of intracellular Ca(2+) concentration. RESULTS: Concentrations of 0...
March 11, 2016: BMC Biochemistry
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