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https://www.readbyqxmd.com/read/28916620/the-anthracycline-metabolite-doxorubicinol-abolishes-ryr2-sensitivity-to-physiological-changes-in-luminal-ca-2-through-an-interaction-with-calsequestrin
#1
Amy Hanna, Alexander Lam, Chris Thekkedam, Hermia Willemse, Angela Fay Dulhunty, Nicole Beard
The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca2+ release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca2+ binding protein calsequestrin2 (CSQ2). Normal increases in RyR2 activity in response to increasing diastolic SR [Ca2+] are influenced by CSQ2 and are disrupted in arrhythmic conditions. Therefore we explored the action of doxOL on RyR2's response to changes in luminal [Ca2+] seen during diastole...
September 15, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28899787/differential-expression-of-ryanodine-receptor-isoforms-after-spinal-cord-injury
#2
Nicolas Pelisch, Cynthia Gomes, Jacqueline M Nally, Jeffrey C Petruska, David P Stirling
Ryanodine receptors (RyRs) are highly conductive intracellular Ca(2+) release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca(2+) overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI...
September 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28875959/downregulation-of-na-ca-2-exchanger-isoform-1-protects-isolated-hearts-by-sevoflurane-postconditioning-but-not-by-delayed-remote-ischemic-preconditioning-in-rats
#3
Yang Yu, Cheng-Hui Zhou, Yun-Tai Yao, Li-Huan Li
Background: Calcium regulatory proteins-L-type Ca(2+) channels (LTCCs), ryanodine receptor 2 (RyR2), and Na(+)/Ca(2+) exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28842436/ca-2-calmodulin-kinase-ii-dependent-regulation-of-atrial-myocyte-late-na-current-ca-2-cycling-and-excitability-a-mathematical-modeling-study
#4
Birce Onal, Daniel Gratz, Thomas J Hund
Atrial fibrillation (AF) affects more than 3 million people per year in the U.S., and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in regulation of persistent "late" sodium current (INa,L) has been identified. While INa,L inhibition is emerging as a potential antiarrhythmic strategy in AF patients, little is known about the mechanism linking INa,L to atrial arrhythmogenesis...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28835222/genome-wide-association-and-targeted-analysis-of-copy-number-variants-with-psoriatic-arthritis-in-german-patients
#5
Steffen Uebe, Maria Ehrlicher, Arif Bülent Ekici, Frank Behrens, Beate Böhm, Georg Homuth, Claudia Schurmann, Uwe Völker, Michael Jünger, Matthias Nauck, Henry Völzke, Heiko Traupe, Michael Krawczak, Harald Burkhardt, André Reis, Ulrike Hüffmeier
BACKGROUND: Psoriatic Arthritis (PsA) is a chronic inflammatory disease of the joints. PsA is etiologically complex, and 11 susceptibility loci have been identified so far. Most of these overlap with loci associated with psoriasis vulgaris (PsV), the most common psoriatic skin manifestation which is also frequently seen in PsA patients. In addition, two copy number variants (CNVs) are associated with PsV, one of which, located within the LCE3 gene cluster, is also associated with PsA...
August 23, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28818208/catecholamine-dependent-%C3%AE-adrenergic-signaling-in-a-pluripotent-stem-cell-model%C3%A2-of-takotsubo-cardiomyopathy
#6
Thomas Borchert, Daniela Hübscher, Celina I Guessoum, Tuan-Dinh D Lam, Jelena R Ghadri, Isabel N Schellinger, Malte Tiburcy, Norman Y Liaw, Yun Li, Jan Haas, Samuel Sossalla, Mia A Huber, Lukas Cyganek, Claudius Jacobshagen, Ralf Dressel, Uwe Raaz, Viacheslav O Nikolaev, Kaomei Guan, Holger Thiele, Benjamin Meder, Bernd Wollnik, Wolfram-Hubertus Zimmermann, Thomas F Lüscher, Gerd Hasenfuss, Christian Templin, Katrin Streckfuss-Bömeke
BACKGROUND: Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. OBJECTIVES: The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28807154/total-internal-reflectance-fluorescence-imaging-of-genetically-engineered-ryanodine-receptor-targeted-ca-2-probes-in-rat-ventricular-myocytes
#7
Sara Pahlavan, Marin Morad
The details of cardiac Ca(2+) signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca(2+) probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca(2+) nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, Kd=150nM, or FKBP-GCaMP6, Kd=240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP,(2)-targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28807150/two-ef-hand-motifs-in-ryanodine-receptor-calcium-release-channels-contribute-to-isoform-specific-regulation-by-calmodulin
#8
Le Xu, Angela C Gomez, Daniel A Pasek, Gerhard Meissner, Naohiro Yamaguchi
The mammalian ryanodine receptor Ca(2+) release channel (RyR) has a single conserved high affinity calmodulin (CaM) binding domain. However, the skeletal muscle RyR1 is activated and cardiac muscle RyR2 is inhibited by CaM at submicromolar Ca(2+). This suggests isoform-specific domains are involved in RyR regulation by CaM. To gain insight into the differential regulation of cardiac and skeletal muscle RyRs by CaM, RyR1/RyR2 chimeras and mutants were expressed in HEK293 cells, and their single channel activities were measured using a lipid bilayer method...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28798077/cardiovascular-susceptibility-to-in-vivo-ischemic-myocardial-injury-in-male-and-female-rat-offspring-exposed-to-prenatal-hypoxia
#9
Amin Shah, Nobutoshi Matsumura, Anita Quon, Jude S Morton, Jason R B Dyck, Sandra T Davidge
Intrauterine growth restriction (IUGR) following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease (CVD) in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring, which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28795720/restoring-calcium-homeostasis-in-diabetic-cardiomyocytes-an-investigation-through-mathematical-modelling
#10
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28789916/flecainide-reduces-ventricular-arrhythmias-in-patients-with-genotype-ryr2-positive-catecholaminergic-polymorphic-ventricular-tachycardia
#11
Fernando Wangüemert Pérez, Julio Salvador Hernández Afonso, María Del Val Groba Marco, Eduardo Caballero Dorta, Luis Álvarez Acosta, Oscar Campuzano Larrea, Guillermo Pérez, Josep Brugada Terradellas, Ramón Brugada Terradellas
INTRODUCTION AND OBJECTIVES: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by polymorphic or bidirectional ventricular arrhythmias (VA) triggered by physical or emotional stress in young people with a structurally normal heart. Beta-blockers are the cornerstone of treatment, while flecainide has recently been incorporated into the therapeutic arsenal. The aim of this study was to report our experience with this drug. METHODS: The cohort included 174 genotype-positive CPVT-patients from 7 families...
August 5, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#12
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28754745/cardiovascular-susceptibility-to-in-vivo-ischemic-myocardial-injury-in-male-and-female-rat-offspring-exposed-to-prenatal-hypoxia
#13
Amin Shah, Nobutoshi Matsumura, Anita Quon, Jude Sally Morton, Jason Dyck, Sandra Thomas Davidge
Intrauterine growth restriction following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia...
July 28, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28740174/plakophilin-2-is-required-for-transcription-of-genes-that-control-calcium-cycling-and-cardiac-rhythm
#14
Marina Cerrone, Jerome Montnach, Xianming Lin, Yan-Ting Zhao, Mingliang Zhang, Esperanza Agullo-Pascual, Alejandra Leo-Macias, Francisco J Alvarado, Igor Dolgalev, Thomas V Karathanos, Kabir Malkani, Chantal J M Van Opbergen, Joanne J A van Bavel, Hua-Qian Yang, Carolina Vasquez, David Tester, Steven Fowler, Fengxia Liang, Eli Rothenberg, Adriana Heguy, Gregory E Morley, William A Coetzee, Natalia A Trayanova, Michael J Ackerman, Toon A B van Veen, Hector H Valdivia, Mario Delmar
Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell-cell adhesion. Mutations in human PKP2 associate with a life-threatening arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mouse to demonstrate that in addition to its role in cell adhesion, PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28740084/ryanodine-receptors-are-part-of-the-myospryn-complex-in-cardiac-muscle
#15
Matthew A Benson, Caroline L Tinsley, Adrian J Waite, Francesca A Carlisle, Steve M M Sweet, Elisabeth Ehler, Christopher H George, F Anthony Lai, Enca Martin-Rendon, Derek J Blake
The Cardiomyopathy-associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713282/the-n-terminal-region-of-the-ryanodine-receptor-affects-channel-activation
#16
Andrea Faltinova, Nataša Tomaskova, Marián Antalik, Jozef Sevcik, Alexandra Zahradnikova
Mutations in the cardiac ryanodine receptor (RyR2), the ion channel responsible for release of calcium ions from intracellular stores into cytoplasm, are the cause of several inherited cardiac arrhythmias. At the molecular level, disease symptoms can be mimicked by domain peptides from mutation-prone regions of RyR2 that bind to RyR2 and activate it. Here we show that the domain peptide DPcpvtN2, corresponding to the central helix of the N-terminal region of RyR2, activates the RyR2 channel. Structural modeling of interaction between DPcpvtN2 and the N-terminal region of RyR2 in the closed and open conformation provided three plausible structures of the complex...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28687594/reduced-threshold-for-store-overload-induced-ca-2-release-is-a-common-defect-of-ryr1-mutations-associated-with-malignant-hyperthermia-and-central-core-disease
#17
COMPARATIVE STUDY
Wenqian Chen, Andrea Koop, Yingjie Liu, Wenting Guo, Jinhong Wei, Ruiwu Wang, David H MacLennan, Robert T Dirksen, Sui Rong Wayne Chen
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), whereas mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding ryanodine receptor (RyR) isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process known as store overload-induced Ca(2+) release (SOICR)...
August 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#18
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28657075/bioinspired-onion-epithelium-like-structure-promotes-the-maturation-of-cardiomyocytes-derived-from-human-pluripotent-stem-cells
#19
Cong Xu, Li Wang, Yue Yu, Fangchao Yin, Xiaoqing Zhang, Lei Jiang, Jianhua Qin
Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function...
August 22, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28638869/reducing-toxicity-and-increasing-efficiency-aconitine-with-liquiritin-and-glycyrrhetinic-acid-regulate-calcium-regulatory-proteins-in-rat-myocardial-cell
#20
Yuyan Zhang, Li Yu, Weifeng Jin, Hongjing Fan, Min Li, Tianmei Zhou, Haitong Wan, Jiehong Yang
BACKGROUND: Compatibility of Radix Aconiti Carmichaeli and Liquorice is known to treat heart diseases such as heart failure and cardiac arrhythmias. This work answers the question that whether the active components (Aconitine, Liquiritin and Glycyrrhetinic Acid) of Radix Aconiti Carmichaeli and Liquorice could result in regulating intracellular calcium homeostasis and calcium cycling, and thereby verifies the therapeutic material basis. MATERIALS AND METHODS: The myocardial cells were divided into twelve groups randomly as control group, Aconitine group, nine different dose groups that orthogonal combined with Aconitine, Liquiritin and Glycyrrhetinic Acid, and Verapamil group...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
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