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Elisa Tikkanen, Jaakko Haverinen, Stuart Egginton, Minna Hassinen, Matti Vornanen
The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored...
November 21, 2016: Journal of Experimental Biology
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, eighteen male (n=14) and female (n=4) runners (VO2-max: 57.3±3.4 ml·min(-1); mean±SD) completed twenty sessions of maintained low-frequency (LF; every fourth day; n=7) or high-frequency (HF; every second day; n=11) SET (intervention period; INT). Before FAM as well as before and after INT, subjects completed a series of running tests and a biopsy from m...
November 17, 2016: Journal of Applied Physiology
Lei Li, Jing Li, Benjamin M Drum, Yi Chen, Haifeng Yin, Xiaoyun Guo, Stephen W Luckey, Merle L Gilbert, G Stanley McKnight, John D Scott, L Fernando Santana, Qinghang Liu
AIMS: Impaired Ca(2 + )cycling and myocyte contractility are a hallmark of heart failure triggered by pathological stress such as hemodynamic overload. The A-Kinase anchoring protein AKAP150 has been shown to coordinate key aspects of adrenergic regulation of Ca(2+ )cycling and excitation-contraction in cardiomyocytes. However, the role of the AKAP150 signalling complexes in the pathogenesis of heart failure has not been investigated. METHODS AND RESULTS: Here we examined how AKAP150 signalling complexes impact Ca(2+ )cycling, myocyte contractility, and heart failure susceptibility following pathological stress...
November 17, 2016: Cardiovascular Research
Lukas Martin, Klemens Horst, Fausto Chiazza, Silvia Oggero, Massimo Collino, Klaus Brandenburg, Frank Hildebrand, Gernot Marx, Christoph Thiemermann, Tobias Schuerholz
An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca(2+)-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression...
November 17, 2016: Scientific Reports
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUND: Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues...
November 15, 2016: Circulation
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
October 10, 2016: Archives of Endocrinology and Metabolism
Ioannis Karagiannidis, Martina Brunner, Christos C Zouboulis
Darier disease/dyskeratosis follicularis is a genodermatosis characterized by brown, oily keratotic papules and plaques in the seborrheic areas of the face and chest. Responsible for the disease are mutations in the ATP2A2 gene, encoding SERCA2, a calcium pump of the sarco-/endoplasmic reticulum. Mechanical trauma, heat, humidity, ultraviolet B radiation, oral corticosteroids and lithium are known trigger factors of the disorder. We report on a 48-year-old German woman with a flare-up of Darier disease under interferon-α-2a (IFNα-2a) therapy with clinical signs of lichen nitidus...
May 2016: Case Reports in Dermatology
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
Susana Cañón, Ricardo Caballero, Adela Herraiz-Martínez, Marta Pérez-Hernández, Begoña López, Felipe Atienza, José Jalife, Leif Hove-Madsen, Eva Delpón, Antonio Bernad
microRNAs (miR) have considerable potential as therapeutic tools in cardiac diseases. Alterations in atrial miR are involved in the development of atrial fibrillation (AF), but the molecular mechanism underlying their contribution to atrial remodeling in chronic atrial fibrillation (CAF) is only partially understood. Here we used miR array to analyze the miR profile of atrial biopsies from sinus rhythm (SR) and CAF patients. qRT-PCR identified a distinctive CAF-miR signature and described conserved miR-208b upregulation in human and ovine AF atrial tissue...
August 18, 2016: Journal of Molecular and Cellular Cardiology
Cheol Yi Hong, Hyun-Ju Lee, Nu-Ri Choi, Sung-Hoon Jung, Manh-Cuong Vo, My Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins...
2016: Experimental & Molecular Medicine
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
Xin Tong, Tatsuyoshi Kono, Emily K Anderson-Baucum, Wataru Yamamoto, Patrick Gilon, Djamel Lebeche, Richard N Day, Gary E Shull, Carmella Evans-Molina
The sarcoendoplasmic reticulum (ER) Ca(2+) ATPase 2 (SERCA2) pump is a P-type ATPase tasked with the maintenance of ER Ca(2+) stores. Whereas β-cell SERCA2 expression is reduced in diabetes, the role of SERCA2 in the regulation of whole-body glucose homeostasis has remained uncharacterized. To this end, SERCA2 heterozygous mice (S2HET) were challenged with a high-fat diet (HFD) containing 45% of kilocalories from fat. After 16 weeks of the HFD, S2HET mice were hyperglycemic and glucose intolerant, but adiposity and insulin sensitivity were not different between HFD-fed S2HET mice and HFD-fed wild-type controls...
October 2016: Diabetes
Kaare Bjerregaard-Andersen, Ellen Østensen, John D Scott, Kjetil Taskén, Jens Preben Morth
A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18γ/δ are found in complex with sarcoendoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease...
August 2016: Acta Crystallographica. Section F, Structural Biology Communications
Sunil Jit R J Logantha, Mathis K Stokke, Andrew J Atkinson, Sanjay R Kharche, Sajida Parveen, Yawer Saeed, Ivar Sjaastad, Ole M Sejersted, Halina Dobrzynski
BACKGROUND: The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) pump is an important component of the Ca(2+)-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. METHODS AND RESULTS: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P < 0...
2016: Frontiers in Physiology
Xin-Xin Shuai, Yi-di Meng, Yong-Xin Lu, Guan-Hua Su, Xiao-Fang Tao, Jun Han, Su-Dan Xu, Ping Luo
BACKGROUND: Relaxin is a peptide hormone which has been demonstrated to be safe and has a therapeutic effect on acute heart failure in clinic trials. However, its effect on diastolic function is still unknown. The aims of the study were to determine whether relaxin could improve the diastolic function in pressure-overloaded rat model and to analyze potential mechanisms. METHODS AND RESULTS: In the present study, a pressure-overloaded rat model induced by transaortic constriction (TAC) was established...
September 1, 2016: International Journal of Cardiology
L Nguy, E Shubbar, M Jernås, I Nookaew, J Lundgren, B Olsson, H Nilsson, G Guron
AIM: Rats with adenine-induced chronic renal failure (A-CRF) develop a reduced rate of relaxation of the thoracic aorta. The aim of this study was to elucidate the mechanisms underlying this abnormality. METHODS: Male Sprague Dawley rats received either chow containing adenine or were pair-fed with normal chow (controls). After 8-14 weeks, arterial function was analysed ex vivo using wire myography and the expression of proteins involved in vascular smooth muscle excitation-contraction coupling in the thoracic aorta was analysed...
December 2016: Acta Physiologica
Antonella De Angelis, Donato Cappetta, Elena Piegari, Barbara Rinaldi, Loreta Pia Ciuffreda, Grazia Esposito, Fiorella Angelica Valeria Ferraiolo, Alessia Rivellino, Rosa Russo, Maria Donniacuo, Francesco Rossi, Konrad Urbanek, Liberato Berrino
BACKGROUND: To investigate the effects of chronic administration of ranolazine (RAN) on experimental model of heart failure with preserved ejection fraction. METHODS: Seven-weeks old Dahl salt-sensitive rats were fed a high salt diet for 5weeks to induce hypertension. Afterwards, rats continued with a high salt diet and were administered either with vehicle or RAN (20mg/kg/die, ip) for the following 8weeks. Control rats were maintained on a low salt diet. RESULTS: While systolic parameters were not altered, diastolic parameters were changed in high salt animals...
August 15, 2016: International Journal of Cardiology
Xiaoqing Yin, Lu Wang, Gang Qin, Hui Luo, Xiao Liu, Fan Zhang, Zhi Ye, Junjie Zhang, E Wang
BACKGROUND: The effects of low concentration of sevoflurane on right ventricular (RV) function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH) have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH. METHODS: Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings...
2016: PloS One
V Guglielmi, A Oosterhof, N C Voermans, R Cardani, J P Molenaar, T H van Kuppevelt, G Meola, B G van Engelen, G Tomelleri, G Vattemi
Sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) pumps play the major role in lowering cytoplasmic calcium concentration in skeletal muscle by catalyzing the ATP-dependent transport of Ca(2+) from the cytosol to the lumen of the sarcoplasmic reticulum (SR). Although SERCA abnormalities have been hypothesized to contribute to the dysregulation of intracellular Ca(2+) homeostasis and signaling in muscle of patients with myotonic dystrophy (DM) and hypothyroid myopathy, the characterization of SERCA pumps remains elusive and their impairment is still unclear...
June 2016: Neuromuscular Disorders: NMD
Hideaki Toki, Osamu Minowa, Maki Inoue, Hiromi Motegi, Yuko Karashima, Ami Ikeda, Hideki Kaneda, Yoshiyuki Sakuraba, Yuriko Saiki, Shigeharu Wakana, Hiroshi Suzuki, Yoichi Gondo, Toshihiko Shiroishi, Tetsuo Noda
Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1-4] and humans to Darier disease (DD) [14-17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162)...
August 5, 2016: Biochemical and Biophysical Research Communications
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