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SERCA2a

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https://www.readbyqxmd.com/read/27899691/high-throughput-spectral-and-lifetime-based-fret-screening-in-living-cells-to-identify-small-molecule-effectors-of-serca
#1
Tory M Schaaf, Kurt C Peterson, Benjamin D Grant, Prachi Bawaskar, Samantha Yuen, Ji Li, Joseph M Muretta, Gregory D Gillispie, David D Thomas
A robust high-throughput screening (HTS) strategy has been developed to discover small-molecule effectors targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA), based on a fluorescence microplate reader that records both the nanosecond decay waveform (lifetime mode) and the complete emission spectrum (spectral mode), with high precision and speed. This spectral unmixing plate reader (SUPR) was used to screen libraries of small molecules with a fluorescence resonance energy transfer (FRET) biosensor expressed in living cells...
November 29, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#2
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27816525/enhanced-nucleoplasmic-ca-2-signaling-in-ventricular-myocytes-from-young-hypertensive-rats
#3
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...
November 3, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27792751/a-decoy-peptide-targeted-to-protein-phosphatase-1-attenuates-degradation-of-serca2a-in-vascular-smooth-muscle-cells
#4
Seung Pil Jang, Jae Gyun Oh, Dong Hoon Kang, Ju Young Kang, Sang Won Kang, Roger J Hajjar, Woo Jin Park
Neointimal growth in the injured vasculature is largely facilitated by the proliferation of vascular smooth muscle cells (VSMC), which associates with reduced sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. The gene transfer-mediated restoration of the SERCA2a level thus attenuates neointimal growth and VSMC proliferation. We previously reported that a peptide targeted to protein phosphatase 1, ψPLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that ψPLB-SE attenuated neointimal growth in balloon-injured rat carotid arteries, and the proliferation and migration of VSMC cultured in high-serum media (synthetic conditions)...
2016: PloS One
https://www.readbyqxmd.com/read/27780728/serca2a-was-serotonylated-and-may-regulate-sino-atrial-node-pacemaker-activity
#5
Qingjie Wang, Dong Wang, Gaoliang Yan, Yong Qiao, Ling Sun, Boqian Zhu, Xin Wang, Chengchun Tang
The modulation of sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of protein serotonylation by intracellular 5-HT during varies physiological actions. Nevertheless, the functional role of protein serotonylation in controlling SAN automaticity is largely unexplored. In this study, we screened the cardiomyocytes proteins and found that sarco(endo)plasmic reticulum Ca ATPase type 2a (SERCA2a) can be serotonylated...
October 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27761848/dexamethasone-induced-cardiac-deterioration-is-associated-with-both-calcium-handling-abnormalities-and-calcineurin-signaling-pathway-activation
#6
Fabiana de Salvi Guimarães, Wilson Max Almeida Monteiro de Moraes, Luis Henrique Marchesi Bozi, Pâmela R Souza, Ednei Luiz Antonio, Danilo Sales Bocalini, Paulo José Ferreira Tucci, Daniel Araki Ribeiro, Patricia Chakur Brum, Alessandra Medeiros
Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days...
October 19, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27747100/altered-left-ventricular-ion-channel-transcriptome-in-a-high-fat-fed-rat-model-of-obesity-insight-into-obesity-induced-arrhythmogenesis
#7
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
https://www.readbyqxmd.com/read/27742792/global-phosphoproteomic-profiling-reveals-perturbed-signaling-in-a-mouse-model-of-dilated-cardiomyopathy
#8
Uros Kuzmanov, Hongbo Guo, Diana Buchsbaum, Jake Cosme, Cynthia Abbasi, Ruth Isserlin, Parveen Sharma, Anthony O Gramolini, Andrew Emili
Phospholamban (PLN) plays a central role in Ca(2+) homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2A (SERCA2A) Ca(2+) pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27723783/increase-in-cardiac-ischemia-reperfusion-injuries-in-opa1-mouse-model
#9
Sophie Le Page, Marjorie Niro, Jérémy Fauconnier, Laura Cellier, Sophie Tamareille, Abdallah Gharib, Arnaud Chevrollier, Laurent Loufrani, Céline Grenier, Rima Kamel, Emmanuelle Sarzi, Alain Lacampagne, Michel Ovize, Daniel Henrion, Pascal Reynier, Guy Lenaers, Delphine Mirebeau-Prunier, Fabrice Prunier
BACKGROUND: Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain. OBJECTIVES: To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. METHODS AND RESULTS: We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates...
2016: PloS One
https://www.readbyqxmd.com/read/27688314/genotype-dependent-and-independent-calcium-signaling-dysregulation-in-human-hypertrophic-cardiomyopathy
#10
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27677409/angptl2-activity-in-cardiac-pathologies-accelerates-heart-failure-by-perturbing-cardiac-function-and-energy-metabolism
#11
Zhe Tian, Keishi Miyata, Tsuyoshi Kadomatsu, Haruki Horiguchi, Hiroyuki Fukushima, Shugo Tohyama, Yoshihiro Ujihara, Takahiro Okumura, Satoshi Yamaguchi, Jiabin Zhao, Motoyoshi Endo, Jun Morinaga, Michio Sato, Taichi Sugizaki, Shunshun Zhu, Kazutoyo Terada, Hisashi Sakaguchi, Yoshihiro Komohara, Motohiro Takeya, Naoki Takeda, Kimi Araki, Ichiro Manabe, Keiichi Fukuda, Kinya Otsu, Jun Wada, Toyoaki Murohara, Satoshi Mohri, Jun K Yamashita, Motoaki Sano, Yuichi Oike
A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice...
September 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27642167/phospholamban-is-concentrated-in-the-nuclear-envelope-of-cardiomyocytes-and-involved-in-perinuclear-nuclear-calcium-handling
#12
Adonis Z Wu, Dongzhu Xu, Na Yang, Shien-Fong Lin, Peng-Sheng Chen, Steven E Cala, Zhenhui Chen
AIMS: Phospholamban (PLB) regulates the cardiac Ca(2+)-ATPase (SERCA2a) in sarcoplasmic reticulum (SR). However, the localization of PLB at subcellular sites outside the SR and possible contributions to Ca(2+) cycling remain unknown. We examined the intracellular distribution of PLB and tested whether a pool of PLB exists in the nuclear envelope (NE) that might regulate perinuclear/nuclear Ca(2+) (nCa(2+)) handling in cardiomyocytes (CMs). METHODS AND RESULTS: Using confocal immunofluorescence microscopy and immunoblot analyses of CMs and CM nuclei, we discovered that PLB was highly concentrated in NE...
September 15, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27641420/gastrodin-pretreatment-impact-on-sarcoplasmic-reticulum-calcium-transport-atpase-serca-and-calcium-phosphate-plb-expression-in-rats-with-myocardial-ischemia-reperfusion
#13
Yufen Li, Xiaomei Wang, Changli Lou
BACKGROUND Calcium overload, inflammation, and apoptosis play important roles in myocardial ischemia-reperfusion injury (MIRI). Gastrodin pretreatment can alleviate MIRI. This study observed sarcoplasmic reticulum calcium transport ATPase (Ca2+-ATPase, SERCA) and calcium phosphate (PLB) protein expression in the ventricular remodeling process after myocardial infarction to explore the effect of gastrodin pretreatment on MIRI. MATERIAL AND METHODS Healthy 7-week-old male SD rats were randomly divided into a sham group (A), a model group (B), and gastrodin pretreatment groups C, D, and E (100, 200, and 400 mg/kg, respectively) with 20 in each group...
September 19, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27602067/short-term-effects-of-%C3%AE-2-ar-blocker-ici-118-551-on-sarcoplasmic-reticulum-serca2a-and-cardiac-function-of-rats-with-heart-failure
#14
Haibin Gong, Yanfei Li, Lei Wang, Qian Lv, Xiuli Wang
The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27591219/resveratrol-protects-against-lipopolysaccharide-induced-cardiac-dysfunction-by-enhancing-serca2a-activity-through-promoting-the-phospholamban-oligomerization
#15
Tao Bai, Xinyue Hu, Yang Zheng, Shudong Wang, Jian Kong, Lu Cai
The bacterial endotoxin lipopolysaccharide (LPS) is a main culprit responsible for cardiac dysfunction in sepsis. This study examined whether resveratrol could protect against LPS-induced cardiac dysfunction by improving the sarcoplasmic endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. Echocardiographic parameters, cardiomyocyte contractile and Ca(2+) transient properties, markers for cardiac inflammation, cell death, and oxidative stress, SERCA2a activity, and the ratios of phospholamban (PLB) monomer to oligomer were measured...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27539860/loss-of-myocardial-retinoic-acid-receptor-%C3%AE-induces-diastolic-dysfunction-by-promoting-intracellular-oxidative-stress-and-calcium-mishandling-in-adult-mice
#16
Sen Zhu, Rakeshwar S Guleria, Candice M Thomas, Amanda Roth, Fnu Gerilechaogetu, Rajesh Kumar, David E Dostal, Kenneth M Baker, Jing Pan
Retinoic acid receptor (RAR) has been implicated in pathological stimuli-induced cardiac remodeling. To determine whether the impairment of RARα signaling directly contributes to the development of heart dysfunction and the involved mechanisms, tamoxifen-induced myocardial specific RARα deletion (RARαKO) mice were utilized. Echocardiographic and cardiac catheterization studies showed significant diastolic dysfunction after 16wks of gene deletion. However, no significant differences were observed in left ventricular ejection fraction (LVEF), between RARαKO and wild type (WT) control mice...
October 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27526788/pleiotropic-effects-of-simvastatin-on-some-calcium-regulatory-and-myofibrillar-proteins-in-ischemic-reperfused-heart-causality-of-statins-cardioprotection
#17
Adrian Szobi, Martin Lichy, Slavka Carnicka, Dezider Pancza, Pavel Svec, Tana Ravingerova, Adriana Adameov
BACKGROUND: It is known that statins possess beneficial cardioprotective effects irrespective of lipid-lowering action and that cardiac injury due ischemia/reperfusion is associated with Ca2+ dysregulation resulting in contractile dysfunction. OBJECTIVE: With this background, we tested a hypothesis that simvastatin influences signaling of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ), a protein kinase regulating both Ca2+ homeostasis and thick filament function, and thereby might underlie the mitigation of ischemia/reperfusion (I/R)-induced cardiac dysfunction...
August 13, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27510531/intracellular-calcium-increases-in-vascular-smooth-muscle-cells-with-progression-of-chronic-kidney-disease-in-a-rat-model
#18
Stacey Dineen Rodenbeck, Chad A Zarse, Mikaela L McKenney-Drake, Rebecca S Bruning, Michael Sturek, Neal X Chen, Sharon M Moe
BACKGROUND: Vascular smooth muscle cells (VSMCs) exhibit phenotypic plasticity, promoting vascular calcification and increasing cardiovascular risk. Changes in VSMC intracellular calcium ([Ca(2+)]i) are a major determinant of plasticity, but little is known about changes in [Ca(2+)]i in chronic kidney disease (CKD). We have previously demonstrated such plasticity in aortas from our rat model of CKD and therefore sought to examine changes in [Ca(2+)]i during CKD progression. MATERIALS AND METHODS: We examined freshly isolated VSMCs from aortas of normal rats, Cy/+ rats (CKD) with early and advanced CKD, and advanced CKD rats treated without and with 3% calcium gluconate (CKD + Ca(2+)) to lower parathyroid hormone (PTH) levels...
August 9, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27501399/assessment-of-myofilament-ca2-sensitivity-underlying-cardiac-excitation-contraction-coupling
#19
Zai Hao Zhao, Chun Li Jin, Ji Hyun Jang, Yu Na Wu, Sung Joon Kim, Hong Hua Jin, Lan Cui, Yin Hua Zhang
Heart failure and cardiac arrhythmias are the leading causes of mortality and morbidity worldwide. However, the mechanism of pathogenesis and myocardial malfunction in the diseased heart remains to be fully clarified. Recent compelling evidence demonstrates that changes in the myofilament Ca(2+) sensitivity affect intracellular Ca(2+) homeostasis and ion channel activities in cardiac myocytes, the essential mechanisms responsible for the cardiac action potential and contraction in healthy and diseased hearts...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27473037/mitogen-activated-protein-kinase-and-intracellular-polyamine-signaling-is-involved-in-trpv1-activation-induced-cardiac-hypertrophy
#20
Mai Chen, Jiajia Xin, Baohui Liu, Liyang Luo, Jiayi Li, Wen Yin, Mingkai Li
BACKGROUND: The transient receptor potential vanilloid type 1 (TRPV1) is expressed in the cardiovascular system, and increased TRPV1 expression has been associated with cardiac hypertrophy. Nevertheless, the role of TRPV1 in the pathogenesis of cardiac hypertrophy and the underlying molecular mechanisms remain unclear. METHODS AND RESULTS: In cultured cardiomyocytes, activation of TRPV1 increased cell size and elevated expression of atrial natriuretic peptide mRNA and intracellular calcium level, which was reversed by TRPV1 antagonist capsazepine...
2016: Journal of the American Heart Association
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