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phospholamban

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https://www.readbyqxmd.com/read/29653363/trapidil-improves-hemodynamic-echocardiographic-and-redox-state-parameters-of-right-ventricle-in-monocrotaline-induced-pulmonary-arterial-hypertension-model
#1
Patrick Türck, Denise Santos Lacerda, Cristina Campos Carraro, Bruna Gazzi de Lima-Seolin, Rayane Brinck Teixeira, Jéssica Hellen Poletto Bonetto, Rafael Colombo, Paulo Cavalheiro Schenkel, Adriane Belló-Klein, Alex Sander da Rosa Araujo
BACKGROUND: Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. HYPOTHESIS: Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. METHODS AND RESULTS: Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil...
April 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29593308/the-anti-cancer-multikinase-inhibitor-sorafenib-impairs-cardiac-contractility-by-reducing-phospholamban-phosphorylation-and-sarcoplasmic-calcium-transients
#2
Christopher Schneider, Markus Wallner, Ewald Kolesnik, Viktoria Herbst, Heinrich Mächler, Martin Pichler, Dirk von Lewinski, Simon Sedej, Peter P Rainer
Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: -25 ± 4%, 10 µM: -29 ± 7%, 30 µM: -43 ± 12%, p < 0...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29587364/baicalein-rescues-delayed-cooling-via-preservation-of-akt-activation-and-akt-mediated-phospholamban-phosphorylation
#3
Zuohui Shao, Sy-Jou Chen, Xiangdong Zhu, Chunpei Lee, Hsien-Hao Huang, Angelo Meliton, Changqing Li, Terry L Vanden Hoek, Jing Li
Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its cardioprotection is diminished when delay in reaching the target temperature occurs. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis G e orgi , possesses antioxidant properties. Therefore, we hypothesized that baicalein can rescue cooling cardioprotection when cooling is delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used to assess cell survival and contractility, respectively...
March 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518932/diazoxide-improves-mitochondrial-connexin-43-expression-in-a-mouse-model-of-doxorubicin-induced-cardiotoxicity
#4
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518186/influence-of-long-term-salt-diets-on-cardiac-ca2-handling-and-contractility-proteins-in-hypertensive-rats
#5
Rebeca Caldeira Machado Berger, Acaris Benetti, Adriana Castello Costa Girardi, Ludimila Forechi, Rafaella Martins de Oliveira, Paula Frizera Vassallo, José Geraldo Mill
BACKGROUND: High sodium intake contributes to the pathogenesis of hypertension and adversely affects cardiac function. Conversely, sodium reduction is associated with a blood pressure decrease and improved cardiovascular function. However, the mechanisms that underlie the cardiac effects induced by salt intake in hypertension have not been fully elucidated. Ca2+ handling is critical for efficient myocardial function; thus, we aimed to investigate the long-term effects of diets with different salt contents on cardiac function and Ca2+ handling proteins in spontaneously hypertensive rats (SHRs)...
March 5, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29501609/effects-of-the-arg9cys-and-arg25cys-mutations-on-phospholamban-s-conformational-equilibrium-in-membrane-bilayers
#6
Sarah E D Nelson, Kim N Ha, Tata Gopinath, Mara H Exline, Alessandro Mascioni, David D Thomas, Gianluigi Veglia
Approximately, 70% of the Ca2+ ion transport into the sarcoplasmic reticulum is catalyzed by the sarcoplasmic reticulum Ca2+ -ATPase (SERCA), whose activity is endogenously regulated by phospholamban (PLN). PLN comprises a TM inhibitory region and a cytoplasmic regulatory region that harbors a consensus sequence for cAMP-dependent protein kinase (PKA). The inhibitory region binds the ATPase, reducing its apparent Ca2+ binding affinity. β-adrenergic stimulation activates PKA, which phosphorylates PLN at Ser 16, reversing its inhibitory function...
March 1, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29464562/the-sarcoendoplasmic-reticulum-calcium-atpase
#7
Joseph O Primeau, Gareth P Armanious, M'Lynn E Fisher, Howard S Young
The calcium pump (a.k.a. Ca2+ -ATPase or SERCA) is a membrane transport protein ubiquitously found in the endoplasmic reticulum (ER) of all eukaryotic cells. As a calcium transporter, SERCA maintains the low cytosolic calcium level that enables a vast array of signaling pathways and physiological processes (e.g. synaptic transmission, muscle contraction, fertilization). In muscle cells, SERCA promotes relaxation by pumping calcium ions from the cytosol into the lumen of the sarcoplasmic reticulum (SR), the main storage compartment for intracellular calcium...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29431258/human-cardiomyocyte-calcium-handling-and-transverse-tubules-in-mid-stage-of-post-myocardial-infarction-heart-failure
#8
Morten Andre Høydal, Idar Kirkeby-Garstad, Asbjørn Karevold, Rune Wiseth, Rune Haaverstad, Alexander Wahba, Tomas L Stølen, Riccardo Contu, Gianluigi Condorelli, Øyvind Ellingsen, Godfrey L Smith, Ole J Kemi, Ulrik Wisløff
AIMS: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. METHODS AND RESULTS: Nine MI patients and eight control patients without MI (non-MI) were included...
February 12, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29407107/protection-against-reperfusion-injury-by-3-4-dihydroxyflavonol-in-rat-isolated-hearts-involves-inhibition-of-phospholamban-and-jnk2
#9
Kai Yee Chin, Lokugan S Silva, Ian A Darby, Dominic C H Ng, Owen L Woodman
BACKGROUND: Flavonols, including 3',4'-dihydroxyflavonol (DiOHF), reduce myocardial ischemia and reperfusion (I/R) injury but their mechanism remains uncertain. To better understand the mechanism of the cardioprotective actions of flavonols we investigated the effect of DiOHF on cardiac function and the activation of protective and injurious signalling kinases after I/R in rat isolated hearts. METHODS: We assessed the effect of global ischemia (20min) and reperfusion (5-30min) on cardiac function and injury in rat isolated, perfused hearts in the absence or presence of DiOHF (10μM) during reperfusion...
March 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29403384/phenotyping-of-mice-with-heart-specific-overexpression-of-a2a-adenosine-receptors-evidence-for-cardioprotective-effects-of-a2a-adenosine-receptors
#10
Peter Boknik, Katharina Drzewiecki, John Eskandar, Ulrich Gergs, Stephanie Grote-Wessels, Larissa Fabritz, Paulus Kirchhof, Frank U Müller, Frank Stümpel, Wilhelm Schmitz, Norbert Zimmermann, Uwe Kirchhefer, Joachim Neumann
Background: Adenosine can be produced in the heart and acts on cardiac adenosine receptors. One of these receptors is the A2A-adenosine receptor (A2A-AR). Methods and Results: To better understand its role in cardiac function, we generated and characterized mice (A2A-TG) which overexpress the human A2A-AR in cardiomyocytes. In isolated atrial preparations from A2A-TG but not from WT, CGS 21680, an A2A-AR agonist, exerted positive inotropic and chronotropic effects. In ventricular preparations from A2A-TG but not WT, CGS 21680 increased the cAMP content and the phosphorylation state of phospholamban and of the inhibitory subunit of troponin in A2A-TG but not WT...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29371236/crabp1-protects-the-heart-from-isoproterenol-induced-acute-and-chronic-remodeling
#11
Sung Wook Park, Shawna D Persaud, Stanislas Ogokeh, Tatyana A Meyers, DeWayne Townsend, Li Na Wei
Excessive and/or persistent activation of calcium-calmodulin protein kinase II (CaMKII) is detrimental in acute and chronic cardiac injury. However, intrinsic regulators of CaMKII activity are poorly understood. We find that cellular retinoic acid binding protein 1 (CRABP1) directly interacts with CaMKII, and uncover a functional role for CRABP1 in regulating CaMKII activation. We generated Crabp1 null mice (CKO) in C57BL/6J background for pathophysiological studies. CKO mice develop hypertrophy as adults, exhibiting significant left ventricular dilation with reduced ejection fraction at the baseline cardiac function...
January 25, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29350681/aav-9-mediated-phosphatase-1-inhibitor-1-overexpression-improves-cardiac-contractility-in-unchallenged-mice-but-is-deleterious-in-pressure-overload
#12
D M Schwab, L Tilemann, R Bauer, M Heckmann, A Jungmann, M Wagner, J Burgis, C Vettel, H A Katus, A El-Armouche, O J Müller
The downregulation of β-adrenergic receptors (β-AR) and decreased cAMP-dependent protein kinase activity in failing hearts results in decreased phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal amplifier element of β-adrenergic signaling, leading to increased protein phosphatase 1 activity and dephosphorylation of key phosphoproteins, including phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to β-AR desensitization; therefore its modulation is a promising approach in heart failure treatment...
January 2018: Gene Therapy
https://www.readbyqxmd.com/read/29325795/insertional-mutagenesis-confounds-the-mechanism-of-the-morbid-phenotype-of-a-pln-r9c-transgenic-mouse-line
#13
Alexander Kraev
BACKGROUND: A mouse line with heterozygous transgenic expression of phospholamban carrying a substitution of cysteine for arginine 9 (TgPLNR9C ) under the control of α-myosin heavy chain (αMHC) promoter features dilated cardiomyopathy, heart failure, and premature death. METHODS AND RESULTS: Determination of transgene chromosomal localization by conventional methods shows that in this line the transgenic array of 13 PLNR9C expression cassettes, arranged in a head-to-tail tandem orientation, have integrated into the bidirectional promoter of the αMHC (Myh6) gene and the gene for the regulatory noncoding RNA Myheart (Mhrt), both of which are known to be involved in cardiac development and pathology...
February 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29273673/reduced-serca-activity-underlies-dysregulation-of-ca-2-homeostasis-under-atmospheric-o-2-levels
#14
Thomas P Keeley, Richard C M Siow, Ron Jacob, Giovanni E Mann
Unregulated increases in cellular Ca2+ homeostasis are a hallmark of pathophysiological conditions and a key trigger of cell death. Endothelial cells cultured under physiologic O2 conditions (5% O2 ) exhibit a reduced cytosolic Ca2+ response to stimulation. The mechanism for reduced plateau [Ca2+ ]i upon stimulation was due to increased sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)-mediated reuptake rather than changes in Ca2+ influx capacity. Agonist-stimulated phosphorylation of the SERCA regulatory protein phospholamban was increased in cells cultured under 5% O2 ...
January 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29191788/progressive-impairment-of-atrial-myocyte-function-during-left-ventricular-hypertrophy-and-heart-failure
#15
Florentina Pluteanu, Yulia Nikonova, Anna Holzapfel, Birgit Herzog, Anna Scherer, Judit Preisenberger, Jelena Plačkić, Katharina Scheer, Teodora Ivanova, Alicja Bukowska, Andreas Goette, Jens Kockskämper
Hypertensive heart disease (HHD) can cause left ventricular (LV) hypertrophy and heart failure (HF). It is unclear, though, which factors may contribute to the transition from compensated LV hypertrophy to HF in HHD. We hypothesized that maladaptive atrial remodeling with impaired atrial myocyte function would occur in advanced HHD and may be associated with the emergence of HF. Experiments were performed on atrial myocytes and tissue from old (15-25months) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with advanced HHD...
January 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29179218/puerarin-enhances-ca2-reuptake-and-ca2-content-of-sarcoplasmic-reticulum-in-murine-embryonic-stem-cell-derived-cardiomyocytes-via-upregulation-of-serca2a
#16
Lu Wang, Yurong Cui, Qinghua Liu, Yuanlong Song, Qinghua Hu, Ming Tang, Jürgen Hescheler, Jiaoya Xi
BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29173803/-1-h-detected-mas-solid-state-nmr-experiments-enable-the-simultaneous-mapping-of-rigid-and-dynamic-domains-of-membrane-proteins
#17
T Gopinath, Sarah E D Nelson, Gianluigi Veglia
Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is emerging as a unique method for the atomic resolution structure determination of native membrane proteins in lipid bilayers. Although13 C-detected ssNMR experiments continue to play a major role, recent technological developments have made it possible to carry out1 H-detected experiments, boosting both sensitivity and resolution. Here, we describe a new set of1 H-detected hybrid pulse sequences that combine through-bond and through-space correlation elements into single experiments, enabling the simultaneous detection of rigid and dynamic domains of membrane proteins...
December 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/29150445/the-antiapoptotic-protein-hax-1-mediates-half-of-phospholamban-s-inhibitory-activity-on-calcium-cycling-and-contractility-in-the-heart
#18
Philip A Bidwell, Kobra Haghighi, Evangelia G Kranias
The antiapoptotic protein HAX-1 (HS-associated protein X-1) localizes to sarcoplasmic reticulum (SR) in the heart and interacts with the small membrane protein phospholamban (PLN), inhibiting the cardiac sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) in the regulation of overall calcium handling and heart muscle contractility. However, because global HAX-1 deletion causes early lethality, how much endogenous HAX-1 contributes to PLN's inhibitory activity on calcium cycling is unknown. We therefore generated a cardiac-specific and inducible knock-out mouse model...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#19
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29119312/when-signalling-goes-wrong-pathogenic-variants-in-structural-and-signalling-proteins-causing-cardiomyopathies
#20
Mehroz Ehsan, He Jiang, Kate L Thomson, Katja Gehmlich
Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies...
August 2017: Journal of Muscle Research and Cell Motility
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