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https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#1
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#2
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28212796/sodium-calcium-exchanger-in-pig-coronary-artery
#3
A K Grover
This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na(+)-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca(2+) concentration and extracellular entry of (45)Ca(2+). All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca(2+) pump SERCA2b whose activity was much greater than that of NCX...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28196740/dpb162-ae-an-inhibitor-of-store-operated-ca-2-entry-can-deplete-the-endoplasmic-reticulum-ca-2-store
#4
Mart Bittremieux, Julia V Gerasimenko, Marleen Schuermans, Tomas Luyten, Eloise Stapleton, Kamil J Alzayady, Humbert De Smedt, David I Yule, Katsuhiko Mikoshiba, Peter Vangheluwe, Oleg V Gerasimenko, Jan B Parys, Geert Bultynck
Store-operated Ca(2+) entry (SOCE), an important Ca(2+) signaling pathway in non-excitable cells, regulates a variety of cellular functions. To study its physiological role, pharmacological tools, like 2-aminoethyl diphenylborinate (2-APB), are used to impact SOCE. 2-APB is one of the best characterized SOCE inhibitors. However, 2-APB also activates SOCE at lower concentrations, while it inhibits inositol 1,4,5-trisphosphate receptors (IP3Rs), sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs) and other ion channels, like TRP channels...
February 1, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28188731/design-in-silico-and-in%C3%A2-vitro-evaluation-of-curcumin-analogues-against-plasmodium-falciparum
#5
Chandrajit Dohutia, Dipak Chetia, Kabita Gogoi, Kishore Sarma
The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca(2+) ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity...
February 7, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28183802/differential-effects-of-anoctamins-on-intracellular-calcium-signals
#6
Inês Cabrita, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V Skryabin, Laura K Schenk, Hermann Pavenstädt, Rainer Schreiber, Karl Kunzelmann
The Ca(2+) activated Cl(-) channel TMEM16A [anoctamin (ANO)1] is homologous to yeast Ist2 and has been shown to tether the cortical endoplasmic reticulum (ER) to the plasma membrane. We therefore examined whether ANO1 and other members of the ANO family affect intracellular Ca(2+) ([Ca(2+)]i) signals. It is shown that expression of ANO1 augments Ca(2+) store release upon stimulation of GPCRs, whereas knockdown of ANO1, or lack of Ano1 expression in Ano1(-/-) animals as shown in an earlier report, inhibits Ca(2+) release...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28179072/orai3-channel-is-the-2-apb-induced-endoplasmic-reticulum-calcium-leak
#7
Daniel Leon-Aparicio, Jonathan Pacheco, Jesus Chavez-Reyes, Jose M Galindo, Jesus Valdes, Luis Vaca, Agustin Guerrero-Hernandez
We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca(2+) leak using synthetic Ca(2+) indicators that report changes in both the cytoplasmic ([Ca(2+)]i) and the luminal ER ([Ca(2+)]ER) Ca(2+) concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca(2+) leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca(2+)]ER but did not decrease the ER Ca(2+) leak after thapsigargin (TG)...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#8
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/28150875/atp2a3-gene-as-an-important-player-for-resveratrol-anticancer-activity-in-breast-cancer-cells
#9
Eduardo Izquierdo-Torres, Gabriela Rodríguez, Iván Meneses-Morales, Angel Zarain-Herzberg
The Ca(2+) -ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca(2+) ] homeostasis by pumping Ca(2+) into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28143888/divergent-mechanisms-leading-to-signaling-dysfunction-in-embryonic-muscle-by-bisphenol-a-and-tetrabromobisphenol-a
#10
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/28143473/chemical-composition-vasorelaxant-antioxidant-and-antiplatelet-effects-of-essential-oil-of-artemisia-campestris-l-from-oriental-morocco
#11
Ikram Dib, Marie-Laure Fauconnier, Marianne Sindic, Fatima Belmekki, Asmae Assaidi, Mohamed Berrabah, Hassane Mekhfi, Mohammed Aziz, Abdelkhaleq Legssyer, Mohamed Bnouham, Abderrahim Ziyyat
BACKGROUND: Artemisia campestris L. (Asteraceae) is a medicinal herb traditionally used to treat hypertension and many other diseases. Hence, this study is aimed to analyze the essential oil of A. campestris L (AcEO) and to investigate the antiplatelet, antioxidant effects and the mechanisms of its vasorelaxant effect. METHODS: The chemical composition of AcEO was elucidated using GC/MS analysis. Then, the antioxidant effect was tested on DPPH radical scavenging and on the prevention of β-carotene bleaching...
January 31, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28137585/saturation-of-serca-s-lipid-annulus-may-protect-against-its-thermal-inactivation
#12
Val Andrew Fajardo, Natalie Trojanowski, Laura M Castelli, Paula M Miotto, Foyinsola Amoye, Wendy E Ward, A Russell Tupling, Paul J LeBlanc
The sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca(2+) into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28131630/the-effect-of-pka-mediated-phosphorylation-of-ryanodine-receptor-on-sr-ca-2-leak-in-ventricular-myocytes
#13
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/28130337/silica-nanoparticles-induce-cardiotoxicity-interfering-with-energetic-status-and-ca2-handling-in-adult-rat-cardiomyocytes
#14
Carlos Enrique Guerrero-Beltrán, Judith Bernal-Ramírez, Omar Lozano, Yuriana Oropeza-Almazán, Elena C Castillo, Jesús Roberto Garza, Noemí García, Jorge Vela, Alejandra García-García, Eduardo Ortega, Guillermo Torre-Amione, Nancy Ornelas-Soto, Gerardo García-Rivas
Recent evidence has shown that nanoparticles that have been used to improve or create new functional properties for common products may pose potential risks to human health. Silicon dioxide (SiO2) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO2-induced toxicity in cultured cardiomyocytes exposed to 7 nm or 670 nm SiO2 particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24 h incubation...
January 27, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28122214/importance-of-altered-levels-of-serca-ip3r-and-ryr-in-vascular-smooth-muscle-cell
#15
Jaijus Pallippadan Johny, Michael J Plank, Tim David
Calcium cycling between the sarcoplasmic reticulum (SR) and the cytosol via the sarco-/endoplasmic reticulum Ca-ATPase (SERCA) pump, inositol-1,4,5-triphosphate receptor (IP3R), and Ryanodine receptor (RyR), plays a major role in agonist-induced intracellular calcium ([Ca(2+)]cyt) dynamics in vascular smooth muscle cells (VSMC). Levels of these calcium handling proteins in SR get altered under disease conditions. We have developed a mathematical model to understand the significance of altered levels of SERCA, IP3R, and RyR on the intracellular calcium dynamics of VSMC and to understand how variation in protein levels that arise due to diabetes contribute to different VSMC behavior and thus vascular disease...
January 24, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28111350/antiarrhythmic-effects-of-interleukin-1-inhibition-after-myocardial-infarction
#16
Nicole M De Jesus, Lianguo Wang, Johnny Lai, Robert R Rigor, Samantha D Francis Stuart, Donald M Bers, Merry L Lindsey, Crystal M Ripplinger
BACKGROUND: Interleukin 1β (IL-1β) is a key regulator of the inflammatory response after myocardial infarction (MI) by modulating immune cell recruitment, cytokine production, and extracellular matrix turnover. Elevated levels of IL-1β are associated with adverse remodeling and inhibition of IL-1 signaling after MI results in improved contractile function. OBJECTIVE: The goal of this study was to determine whether IL-1 signaling also contributes to post-MI arrhythmogenesis...
January 19, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28093226/conformational-transitions-and-alternating-access-mechanism-in-the-sarcoplasmic-reticulum-calcium-pump
#17
Avisek Das, Huan Rui, Robert Nakamoto, Benoît Roux
Ion pumps are integral membrane proteins responsible for transporting ions against concentration gradients across biological membranes. Sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), a member of the P-type ATPases family, transports two calcium ions per hydrolyzed ATP molecule via an "alternating-access" mechanism. High-resolution crystallographic structures provide invaluable insight on the structural mechanism of the ion pumping process. However, to understand the molecular details of how ATP hydrolysis is coupled to calcium transport, it is necessary to gain knowledge about the conformational transition pathways connecting the crystallographically resolved conformations...
January 16, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28028837/a-novel-mechanism-of-tandem-activation-of-ryanodine-receptors-by-cytosolic-and-sr-luminal-ca-during-excitation-contraction-coupling-in-atrial-myocytes
#18
Joshua T Maxwell, Lothar A Blatter
In atrial myocytes Ca release during excitation-contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca store into the peripheral subsarcolemmnal junctional (j-SR) and the much more abundant central non-junctional (nj-SR) SR. Action potential (AP)-induced Ca entry activates Ca-induced Ca release (CICR) from j-SR ryanodine receptor (RyR) Ca release channels. Peripheral elevation of [Ca]i initiates CICR from nj-SR and sustains propagation of CICR to the cell centre...
December 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27994552/exercise-training-attenuates-right-ventricular-remodeling-in-rats-with-pulmonary-arterial-stenosis
#19
Brunno Lemes de Melo, Stella S Vieira, Ednei L Antônio, Luís F N Dos Santos, Leslie A Portes, Regiane S Feliciano, Helenita A de Oliveira, José A Silva, Paulo de Tarso C de Carvalho, Paulo J F Tucci, Andrey J Serra
Introduction: Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27992670/dissection-of-the-effects-of-quercetin-on-mouse-myocardium
#20
Michel Santana Santos, Evaleide Diniz de Oliveira, Artur Santos-Miranda, Jader Santos Cruz, Antônio Nei Santana Gondim, José Evaldo Rodrigues de Menezes-Filho, Diego Santos de Souza, Leidiane Pinho-da-Silva, Itamar Couto Guedes de Jesus, Danilo Roman-Campos, Silvia Guatimosim, Aline Lara, Eduardo Antônio Conde-Garcia, Carla Maria Lins de Vasconcelos
Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
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