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Agnieszka Młynarska, Rafał Młynarski, Krzysztof S Gołba, Maciej Sosnowski
BACKGROUND: We hypothesized that small differences in the anatomy of the coronary venous tree might be one of the factors responsible for the differences in the respond for cardiac resynchronization depending on a patient's gender. METHODS: The cardiac computed tomography scans with retrospective gating were performed on 315 subjects (aged 58.3 ± 11.6; 117 women) according to the clinical criteria. The standard protocol for coronary arteries was used during scanning...
October 17, 2016: Kardiologia Polska
Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
Joseph Michael Autry, David D Thomas, L Michel Espinoza-Fonseca
We have performed μs molecular dynamics simulation (MDS) to identify structural mechanisms for sarcolipin (SLN) uncoupling of Ca(2+) transport from ATP hydrolysis for the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). SLN regulates muscle metabolism and energy expenditure to provide resistance against diet-induced obesity and extreme cold. MDS demonstrates that the cytosolic domain of SLN induces a salt bridge-mediated structural rearrangement in the energy-transduction domain of SERCA. We propose that this structural change uncouples SERCA by perturbing Ca(2+) occlusion at residue E309 in transport site II, thus facilitating cytosolic Ca(2+) backflux...
October 12, 2016: Biochemistry
Joachim Behar, Ambhighainath Ganesan, Jin Zhang, Yael Yaniv
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation)...
2016: Frontiers in Physiology
Ryo Ushioda, Akitoshi Miyamoto, Michio Inoue, Satoshi Watanabe, Masaki Okumura, Ken-Ichi Maegawa, Kaiku Uegaki, Shohei Fujii, Yasuko Fukuda, Masataka Umitsu, Junichi Takagi, Kenji Inaba, Katsuhiko Mikoshiba, Kazuhiro Nagata
Calcium ion (Ca(2+)) is an important second messenger that regulates numerous cellular functions. Intracellular Ca(2+) concentration ([Ca(2+)]i) is strictly controlled by Ca(2+) channels and pumps on the endoplasmic reticulum (ER) and plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase (SERCA), imports Ca(2+) from the cytosol into the ER in an ATPase activity-dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is negatively regulated by disulfide bond formation between two luminal cysteines...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Felix Hohendanner, Jaime DeSantiago, Frank R Heinzel, Lothar A Blatter
We tested the hypothesis that in atrial myocytes from a rabbit left ventricular heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca removal during excitation-contraction coupling together with increased Na/Ca exchange (NCX) activity generates a substrate for proarrhythmic Ca release. Ca removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via NCX exclusively in the cell periphery since rabbit atrial myocytes lack transverse tubules. Ca removal kinetics were assessed by the time constant τ of decay of local peripheral subsarcolemmal (SS) and central (CT) action potential (AP) induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo-4)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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 (PLN), calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM compared to controls...
September 29, 2016: Circulation
Alex Gutterres Taranto, Sônia Carine Cova Costa, Franco Henrique Andrade Leite, Matheus Santos de Sá, Milena Botelho Pereira Soares, Miriam Moreira Mussi, Alexsandro Branco
The antiplasmodial active extract of Xanthium cavanillesii contains 3,4-dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and 1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to investigate the interaction of these molecules with a promising validated target of Plasmodium, PfATP6 orthologue of mammalian Ca(+2)-ATPase. Models of this receptor were obtained through comparative modelling. Afterwards, molecular docking studies were used to identify possible interaction modes of these caffeoyl quinic derivatives on the binding site...
August 13, 2016: Natural Product Research
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
Daniel J Blackwell, Taylor J Zak, Seth L Robia
The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers...
September 20, 2016: Biophysical Journal
Trong Tuan Dao, Pankaj Sehgal, Truong Thanh Tung, Jesper Vuust Møller, John Nielsen, Michael Palmgren, Søren Brøgger Christensen, Anja Thoe Fuglsang
P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs. In this work a library of natural compounds was screened and we first identified curcuminoids as plasma membrane H+-ATPases inhibitors in plant and fungal cells. We also found that some of the commercial curcumins contain several curcuminoids...
2016: PloS One
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
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
Asha Hewarathna, Elena Dremina, Christian Schöneich
An interaction of Bcl-2 with SERCA had been documented in vitro using the SERCA1a isoform isolated from rat skeletal muscle [Dremina, E. S., Sharov, V. S., Kumar, K., Azidi, A., Michaelis, E. K., Schöneich, C. (2004) Biochem. J. 383( 361-370)]. Here, we demonstrate the interaction of Bcl-2 with the SERCA3b isoform both in vitro and in cell culture. In vitro, the interaction of Bcl-2 with SERCA3b was studied using Bcl-2∆21, a truncated form of human Bcl-2, and microsomes isolated from SERCA3b-overexpressing HEK-293 cells...
September 14, 2016: Biochimica et Biophysica Acta
Meghna Pant, Naresh C Bal, Muthu Periasamy
Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis and heat production, and contributes to temperature homeostasis...
September 13, 2016: Trends in Endocrinology and Metabolism: TEM
Yuan Liu, Xue-Chun Wang, Dan Hu, Shu-Ran Huang, Qing-Shu Li, Zhi Li, Yan Qu
Heat shock protein 70 (HSP70) maintains Ca(2+) homeostasis in PC12 cells, which may protect against apoptosis; however, the mechanisms of neuroprotection are unclear. Therefore, in this study, we examined Ca(2+) levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct, and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury. HSP70 overexpression increased neuronal viability and ATPase activity, and it decreased cellular reactive oxygen species levels and intracellular Ca(2+) concentration after hypoxia/reoxygenation...
July 2016: Neural Regeneration Research
Saak Victor Ovsepian, Lidia Blazquez-Llorca, Susana Valero Freitag, Eva Ferreira Rodrigues, Jochen Herms
Synaptic dysfunctions and altered neuronal activity play major role in the pathophysiology of Alzheimer's disease (AD), with underlying mechanisms largely unknown. We report that in the prefrontal cortex of amyloid precursor protein-presenilin 1 and APP23 AD mice, baseline activity of pyramidal cells is disrupted by episodes of paroxysmal hyperactivity. Induced by spontaneous EPSC bursts, these incidents are prevalent in neurons proximal to amyloid plaques and involve enhanced activity of glutamate with metabotropic effects...
September 6, 2016: Cerebral Cortex
Sachiko Yamamoto, Munenori Takehara, Makoto Ushimaru
BACKGROUND: SERCA maintains intracellular Ca(2+) homeostasis by sequestering cytosolic Ca(2+) into SR/ER stores. Two primary fatty acid amides (PFAAs), oleamide (18:1(9-cis)) and linoleamide (18:2(9,12-cis)), induce an increase in intracellular Ca(2+) levels, which might be caused by their inhibition of SERCA. METHODS: Three major SERCA isoforms, rSERCA1a, hSERCA2b, and hSERCA3a, were individually overexpressed in COS-1 cells, and the inhibitory action of PFAAs on Ca(2+)-ATPase activity of SERCA was examined...
September 3, 2016: Biochimica et Biophysica Acta
Haidong Yao, Ruifeng Fan, Xia Zhao, Wenchao Zhao, Wei Liu, Jie Yang, Hamid Sattar, Jinxin Zhao, Ziwei Zhang, Shiwen Xu
Selenium (Se) deficiency induces Ca2+ leak and calcification in mammal skeletal muscles; however, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and selenoprotein W (SelW) gene knockdown myoblast and embryo models were used to study the mechanism. The results showed that Se deficiency-induced typical muscular injuries accompanied with Ca2+ leak and oxidative stress (P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P < 0...
August 20, 2016: Oncotarget
Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Jérôme Frenette
The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles...
May 30, 2016: Receptors & Clinical Investigation
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